Trial Outcomes & Findings for Safety and Efficacy Study of Autologous Concentrated Bone Marrow Aspirate (cBMA) for Critical Limb Ischemia (CLI) (NCT NCT01049919)

NCT ID: NCT01049919

Last Updated: 2021-05-28

Results Overview

Occurrence of major amputation (above the ankle joint) or death.

• Recruitment status: TERMINATED
• Study phase: NA
• Target enrollment: 153 participants
• Primary outcome timeframe: 52 weeks
• Results posted on: 2021-05-28

Participant Flow

Enrollment in the study occurred between June 2010 and June 2015. Until February 2014, participants completing the initial 52-week follow-up period could choose to have their second limb randomized if the participant and limb continued to meet all study inclusion and exclusion criteria. Three (3) limbs were enrolled during this time, resulting in a total of 155 limbs in 152 participants that were included in the final intent-to treat analysis for the primary endpoint.

Participants that provided informed consent, completed all screening assessments, and met all inclusion and exclusion criteria for the study went on to be randomized and undergo the study procedure.

Unit of analysis: Limbs

Participant milestones

Measure	Concentrated Bone Marrow Aspirate (cBMA) Bone marrow concentration device: Concentration of autologous bone marrow aspirate for intramuscular delivery to affected limb	Placebo Control (Sham) Placebo procedure (sham): Sham bone marrow aspiration, sham delivery to affected limb
Overall Study STARTED	117 119	36 36
Overall Study COMPLETED	65 67	19 19
Overall Study NOT COMPLETED	52 52	17 17

Reasons for withdrawal

Measure	Concentrated Bone Marrow Aspirate (cBMA) Bone marrow concentration device: Concentration of autologous bone marrow aspirate for intramuscular delivery to affected limb	Placebo Control (Sham) Placebo procedure (sham): Sham bone marrow aspiration, sham delivery to affected limb
Overall Study Met study endpoint (major amputation, death)	36	16
Overall Study Withdrawal by Subject	5	0
Overall Study Lost to Follow-up	6	1
Overall Study Physician Decision	2	0
Overall Study Received 2nd treatment via compassionate use	1	0
Overall Study Early study termination by sponsor.	2	0

Baseline Characteristics

Safety and Efficacy Study of Autologous Concentrated Bone Marrow Aspirate (cBMA) for Critical Limb Ischemia (CLI)

Baseline characteristics by cohort

Measure	Concentrated Bone Marrow Aspirate (cBMA) n=119 Limbs Bone marrow concentration device: Concentration of autologous bone marrow aspirate for intramuscular delivery to affected limb	Placebo Control (Sham) n=36 Limbs Placebo procedure (sham): Sham bone marrow aspiration, sham delivery to affected limb	Total n=155 Limbs Total of all reporting groups
Age, Continuous	64.7 years STANDARD_DEVIATION 11.9 • n=119 Limbs	66.7 years STANDARD_DEVIATION 12.2 • n=36 Limbs	65.0 years STANDARD_DEVIATION 11.9 • n=155 Limbs
Sex: Female, Male Female	48 Limbs n=119 Limbs	16 Limbs n=36 Limbs	64 Limbs n=155 Limbs
Sex: Female, Male Male	71 Limbs n=119 Limbs	20 Limbs n=36 Limbs	91 Limbs n=155 Limbs
Race/Ethnicity, Customized African-American	24 Limbs n=119 Limbs	4 Limbs n=36 Limbs	28 Limbs n=155 Limbs
Race/Ethnicity, Customized White (non-Hispanic)	91 Limbs n=119 Limbs	27 Limbs n=36 Limbs	118 Limbs n=155 Limbs
Race/Ethnicity, Customized White (Hispanic)	3 Limbs n=119 Limbs	4 Limbs n=36 Limbs	7 Limbs n=155 Limbs
Race/Ethnicity, Customized Other	1 Limbs n=119 Limbs	1 Limbs n=36 Limbs	2 Limbs n=155 Limbs
Region of Enrollment United States	117 participants n=5 Participants	36 participants n=7 Participants	153 participants n=5 Participants
Rutherford Score Rutherford Score = 4	65 Limbs n=119 Limbs	19 Limbs n=36 Limbs	84 Limbs n=155 Limbs
Rutherford Score Rutherford Score = 5	54 Limbs n=119 Limbs	17 Limbs n=36 Limbs	71 Limbs n=155 Limbs
Diabetic Status Diabetes = Yes	49 Limbs n=119 Limbs	14 Limbs n=36 Limbs	63 Limbs n=155 Limbs
Diabetic Status Diabetes = No	70 Limbs n=119 Limbs	22 Limbs n=36 Limbs	92 Limbs n=155 Limbs

PRIMARY outcome

Timeframe: 52 weeks

Population: All limbs that were randomized to a treatment group were included in the analysis for the primary endpoint.

Occurrence of major amputation (above the ankle joint) or death.

Outcome measures

Measure	Concentrated Bone Marrow Aspirate (cBMA) n=119 Limbs Bone marrow concentration device: Concentration of autologous bone marrow aspirate for intramuscular delivery to affected limb	Placebo Control (Sham) n=36 Participants Placebo procedure (sham): Sham bone marrow aspiration, sham delivery to affected limb
Occurrence of Major Amputation or Death	24 Limbs	11 Limbs

SECONDARY outcome

Timeframe: 52 weeks

Population: All limbs that were randomized to a treatment group, did not meet a primary endpoint or otherwise exit from the study, and that had an assessment available at 52 weeks were included in the analysis.

Pain reported at the 52-week follow-up visit as assessed on the visual analog scale (VAS). Scores are recorded by making a handwritten mark on a 10-cm line that represents a continuum between "no pain" and "worst pain." The distance from the beginning of the line is measured and reported in centimeters (cm), with 0 representing no pain and 10 representing the worst possible pain.

Outcome measures

Measure	Concentrated Bone Marrow Aspirate (cBMA) n=119 Limbs Bone marrow concentration device: Concentration of autologous bone marrow aspirate for intramuscular delivery to affected limb	Placebo Control (Sham) n=36 Limbs Placebo procedure (sham): Sham bone marrow aspiration, sham delivery to affected limb
Visual Analog Scale (VAS) - Pain Baseline	6.462 score on a scale Standard Deviation 7.789	5.836 score on a scale Standard Deviation 2.680
Visual Analog Scale (VAS) - Pain 52 Weeks	3.651 score on a scale Standard Deviation 2.964	3.346 score on a scale Standard Deviation 3.019

SECONDARY outcome

Timeframe: 52 weeks

Population: All limbs that were randomized to a treatment group, did not meet a primary endpoint or otherwise exit from the study, and that had an assessment available at 52 weeks were included in the analysis.

Measurement (in meters) of the total distance a participant is able to walk in 6 minutes. Since ability to walk is related to the condition of the affected limb, this measure is tied to limb pain and function. If a participant had multiple limbs included in the study, each limb was evaluated separately. Only one limb could be included in the study at a time.

Outcome measures

Measure	Concentrated Bone Marrow Aspirate (cBMA) n=119 Limbs Bone marrow concentration device: Concentration of autologous bone marrow aspirate for intramuscular delivery to affected limb	Placebo Control (Sham) n=36 Limbs Placebo procedure (sham): Sham bone marrow aspiration, sham delivery to affected limb
Six-Minute Walk Test Baseline	158.508 meters Standard Deviation 115.157	173.114 meters Standard Deviation 130.397
Six-Minute Walk Test 52 Weeks	223.545 meters Standard Deviation 170.015	218.352 meters Standard Deviation 148.226

OTHER_PRE_SPECIFIED outcome

Timeframe: 5 years

Population: All randomized participants were included in the analysis. Some participants did not re-consent for follow-up after 52 weeks and as such their long-term status is unknown. For the purposes of this analysis, they are counted with those who completed follow-up. Control participants that received crossover therapy with cBMA after 52 weeks are counted with the control group.

Occurrence of major amputation (above the ankle joint) or death for all participants through final follow-up.

Outcome measures

Measure	Concentrated Bone Marrow Aspirate (cBMA) n=119 Limbs Bone marrow concentration device: Concentration of autologous bone marrow aspirate for intramuscular delivery to affected limb	Placebo Control (Sham) n=36 Limbs Placebo procedure (sham): Sham bone marrow aspiration, sham delivery to affected limb
Occurrence of Major Amputation or Death	36 Limbs	16 Limbs

POST_HOC outcome

Timeframe: 52 weeks

Population: All limbs for subjects from the following subgroups that were randomized to a treatment group were included in this post-hoc analysis: Rutherford Category 4 and diabetic, Rutherford Category 4 and non-diabetic, Rutherford Category 5 and non-diabetic.

Occurrence of major amputation (above the ankle joint) or death, excluding the subgroup of subjects with Rutherford Category 5 critical limb ischemia and diabetes.

The Rutherford score is a classification of severity for peripheral artery disease which ranges from 0 (asymptomatic) to 6 (major tissue loss extending above the transmetatarsal level, functional foot no longer salvageable). The study enrolled participants with Rutherford scores of 4 (ischemic rest pain) and 5 (minor tissue loss, nonhealing ulcer, and/or focal dry gangrene).

Outcome measures

Measure	Concentrated Bone Marrow Aspirate (cBMA) n=94 Limbs Bone marrow concentration device: Concentration of autologous bone marrow aspirate for intramuscular delivery to affected limb	Placebo Control (Sham) n=30 Limbs Placebo procedure (sham): Sham bone marrow aspiration, sham delivery to affected limb
Occurrence of Major Amputation or Death, Excluding Rutherford 5 Diabetic Subjects	13 Limbs	10 Limbs

Adverse Events

Concentrated Bone Marrow Aspirate (cBMA)

Serious events: 66 serious events

Other events: 117 other events

Deaths: 11 deaths

Placebo Control (Sham)

Serious events: 24 serious events

Other events: 35 other events

Deaths: 7 deaths

Serious adverse events

Measure	Concentrated Bone Marrow Aspirate (cBMA) n=119 participants at risk Bone marrow concentration device: Concentration of autologous bone marrow aspirate for intramuscular delivery to affected limb	Placebo Control (Sham) n=36 participants at risk Placebo procedure (sham): Sham bone marrow aspiration, sham delivery to affected limb
Surgical and medical procedures Major Amputation - Index Leg	16.0% 19/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	22.2% 8/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Musculoskeletal and connective tissue disorders Pain - Index Leg	5.9% 7/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	16.7% 6/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Infections and infestations Cellulitis - Index Leg	5.9% 7/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	8.3% 3/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
General disorders Death	4.2% 5/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	8.3% 3/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Vascular disorders Ischemia - Index Leg	3.4% 4/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	8.3% 3/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Surgical and medical procedures Toe Amputation - Index Leg	4.2% 5/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	5.6% 2/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Skin and subcutaneous tissue disorders Gangrene - Index Leg	5.9% 7/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	0.00% 0/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Infections and infestations Pneumonia	5.0% 6/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	2.8% 1/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Respiratory, thoracic and mediastinal disorders Respiratory Failure	0.84% 1/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	11.1% 4/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Cardiac disorders Acute Congestive Heart Failure	2.5% 3/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	5.6% 2/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Skin and subcutaneous tissue disorders Wound - Index Leg	4.2% 5/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	2.8% 1/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Infections and infestations Infection - Index Leg	3.4% 4/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	0.00% 0/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Renal and urinary disorders Acute Kidney Injury	0.84% 1/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	5.6% 2/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Surgical and medical procedures Bypass Graft - Index Leg	0.84% 1/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	5.6% 2/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Cardiac disorders Chest Pain	2.5% 3/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	8.3% 3/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Gastrointestinal disorders Gastrointestinal Bleed	0.84% 1/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	5.6% 2/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Blood and lymphatic system disorders Low Red Blood Cell-Related Level	1.7% 2/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	2.8% 1/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Vascular disorders Stroke	1.7% 2/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	2.8% 1/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Infections and infestations Osteomyelitis - Index Leg	3.4% 4/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	0.00% 0/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Skin and subcutaneous tissue disorders Ulceration - Index Leg	0.00% 0/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	5.6% 2/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Infections and infestations Sepsis	0.84% 1/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	2.8% 1/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Skin and subcutaneous tissue disorders Wound - Contralateral Leg	0.84% 1/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	2.8% 1/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Gastrointestinal disorders Ischemic Bowel	1.7% 2/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	0.00% 0/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Gastrointestinal disorders Nausea/Vomiting	1.7% 2/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	0.00% 0/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
General disorders Abdominal Pain	1.7% 2/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	0.00% 0/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Surgical and medical procedures Amputation of Foot - Contralateral Foot	0.00% 0/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	2.8% 1/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Surgical and medical procedures Amputation of Toe - Contralateral Leg	0.00% 0/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	2.8% 1/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Immune system disorders Anaphylaxis Related to Antibiotic	0.00% 0/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	2.8% 1/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Gastrointestinal disorders Gastric Ulcer	0.00% 0/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	2.8% 1/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Renal and urinary disorders Hematuria	0.00% 0/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	2.8% 1/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Blood and lymphatic system disorders Hemorrhagic Anemia	0.00% 0/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	2.8% 1/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Metabolism and nutrition disorders Hypomagnesemia	0.00% 0/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	2.8% 1/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Surgical and medical procedures Major Amputation - Contralateral Leg	0.00% 0/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	2.8% 1/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Vascular disorders Non-ST-Elevation Myocardial Infarction	0.00% 0/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	2.8% 1/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Vascular disorders Shock	0.00% 0/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	2.8% 1/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
General disorders General Weakness	0.00% 0/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	2.8% 1/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Metabolism and nutrition disorders Weakness - Hand	0.00% 0/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	2.8% 1/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Cardiac disorders Atrial Fibrillation	1.7% 2/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	0.00% 0/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Infections and infestations Abdominal Sepsis/Shock	0.84% 1/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	0.00% 0/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Skin and subcutaneous tissue disorders Abscess - Buttock	0.84% 1/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	0.00% 0/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Surgical and medical procedures Angioplasty - Contralateral Leg	0.84% 1/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	0.00% 0/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Surgical and medical procedures Angioplasty - Index Leg	0.84% 1/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	0.00% 0/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Cardiac disorders Asystole Episode	0.84% 1/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	0.00% 0/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Infections and infestations Bacteremia	0.84% 1/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	0.00% 0/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Cardiac disorders Bradycardia	0.84% 1/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	0.00% 0/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Cardiac disorders Cardiac Decompensation	0.84% 1/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	0.00% 0/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Vascular disorders Cardiac Ischemia	0.84% 1/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	0.00% 0/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Vascular disorders Carotid Blockage	0.84% 1/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	0.00% 0/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Infections and infestations Cellulitis - Arm	0.84% 1/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	0.00% 0/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Infections and infestations Cellulitis - Bilateral Legs	0.84% 1/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	0.00% 0/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Infections and infestations Cellulitis - Contralateral Leg	0.84% 1/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	0.00% 0/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Hepatobiliary disorders Cholelithiasis	0.84% 1/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	0.00% 0/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Vascular disorders Deep Vein Thrombosis - Index Leg	0.84% 1/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	0.00% 0/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Vascular disorders Deconditioning	0.84% 1/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	0.00% 0/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Musculoskeletal and connective tissue disorders Degenerative Disc - Cervical Spine	0.84% 1/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	0.00% 0/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Metabolism and nutrition disorders Diabetic Ketoacidosis	0.84% 1/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	0.00% 0/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Surgical and medical procedures Elective Surgery	0.84% 1/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	0.00% 0/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Injury, poisoning and procedural complications Fall	0.84% 1/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	0.00% 0/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Reproductive system and breast disorders Fibroids	0.84% 1/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	0.00% 0/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Injury, poisoning and procedural complications Fracture - Contralateral Leg	0.84% 1/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	0.00% 0/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
General disorders Hematoma	0.84% 1/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	0.00% 0/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Investigations Hyperglycemia	0.84% 1/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	0.00% 0/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Metabolism and nutrition disorders Hyperkalemia	0.84% 1/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	0.00% 0/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Gastrointestinal disorders Ileocolic Anastomotic Leak	0.84% 1/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	0.00% 0/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Infections and infestations Infected Abdominal Mesh	0.84% 1/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	0.00% 0/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Infections and infestations Infection - Contralateral Leg	0.84% 1/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	0.00% 0/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Infections and infestations Intra-Abdominal Abscess	0.84% 1/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	0.00% 0/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Surgical and medical procedures Knee Revision - Index Leg	0.84% 1/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	0.00% 0/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Gastrointestinal disorders Large Bowel Obstruction	0.84% 1/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	0.00% 0/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Cardiac disorders Myocardial Infarction	0.84% 1/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	0.00% 0/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Melanoma	0.84% 1/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	0.00% 0/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Reproductive system and breast disorders Menstruation	0.84% 1/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	0.00% 0/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Investigations Metabolic Acidosis	0.84% 1/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	0.00% 0/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Vascular disorders Near Syncope	0.84% 1/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	0.00% 0/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
General disorders Non-Healing of Toe Amputation Site	0.84% 1/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	0.00% 0/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Infections and infestations Osteomyelitis - Contralateral Leg	0.84% 1/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	0.00% 0/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Nervous system disorders Oversedation	0.84% 1/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	0.00% 0/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Musculoskeletal and connective tissue disorders Pain - Contralateral Leg	0.84% 1/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	0.00% 0/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Vascular disorders Peripheral Artery Disease	0.84% 1/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	0.00% 0/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Infections and infestations Urinary Tract Infection	0.84% 1/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	0.00% 0/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
General disorders Prolonged Hospitalization	0.84% 1/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	0.00% 0/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Vascular disorders Superior Mesenteric Artery Thrombus	0.84% 1/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	0.00% 0/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Cardiac disorders Shortness of Breath	0.84% 1/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	0.00% 0/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Vascular disorders Stenosis of Bypass Graft - Index Leg	0.84% 1/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	0.00% 0/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Injury, poisoning and procedural complications Subarachnoid Hemorrhage	0.84% 1/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	0.00% 0/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Vascular disorders Syncope	0.84% 1/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	0.00% 0/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Skin and subcutaneous tissue disorders Ulceration - Contralateral Leg	0.84% 1/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	0.00% 0/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Renal and urinary disorders Urinary Retention	0.84% 1/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	0.00% 0/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Vascular disorders Venous Thromboembolism - Contralateral Leg	0.84% 1/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	0.00% 0/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.

Other adverse events

Measure	Concentrated Bone Marrow Aspirate (cBMA) n=119 participants at risk Bone marrow concentration device: Concentration of autologous bone marrow aspirate for intramuscular delivery to affected limb	Placebo Control (Sham) n=36 participants at risk Placebo procedure (sham): Sham bone marrow aspiration, sham delivery to affected limb
Blood and lymphatic system disorders Low Red Blood Cell-Related Level	73.1% 87/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	36.1% 13/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Musculoskeletal and connective tissue disorders Pain - Index Leg	52.1% 62/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	61.1% 22/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
General disorders Pain - Bilateral Iliac Crests	25.2% 30/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	11.1% 4/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Skin and subcutaneous tissue disorders Ulceration - Index Leg	14.3% 17/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	22.2% 8/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Blood and lymphatic system disorders Low White Blood Cell-Related Level	14.3% 17/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	13.9% 5/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Infections and infestations Cellulitis - Index Leg	11.8% 14/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	11.1% 4/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Skin and subcutaneous tissue disorders Erythema - Index Leg	7.6% 9/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	13.9% 5/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Metabolism and nutrition disorders Edema - Index Leg	10.1% 12/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	5.6% 2/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Blood and lymphatic system disorders High White Blood Cell-Related Level	9.2% 11/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	5.6% 2/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Gastrointestinal disorders Nausea/Vomiting	6.7% 8/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	11.1% 4/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Musculoskeletal and connective tissue disorders Pain - Back	8.4% 10/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	5.6% 2/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Skin and subcutaneous tissue disorders Wound - Index Leg	12.6% 15/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	19.4% 7/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Infections and infestations Pneumonia	5.9% 7/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	8.3% 3/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Skin and subcutaneous tissue disorders Gangrene - Index Leg	7.6% 9/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	2.8% 1/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Infections and infestations Infection - Index Leg	8.4% 10/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	0.00% 0/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Infections and infestations Respiratory Infection	3.4% 4/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	8.3% 3/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Blood and lymphatic system disorders High Red Blood Cell-Related Level	4.2% 5/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	5.6% 2/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Infections and infestations Urinary Tract Infection	4.2% 5/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	5.6% 2/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Renal and urinary disorders Urinary Retention	5.0% 6/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	2.8% 1/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
General disorders Fever	1.7% 2/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	11.1% 4/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Cardiac disorders Acute Congestive Heart Failure	3.4% 4/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	5.6% 2/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Renal and urinary disorders Acute Kidney Injury	3.4% 4/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	5.6% 2/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Metabolism and nutrition disorders Hyperglycemia	5.0% 6/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	0.00% 0/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Nervous system disorders Dizziness	2.5% 3/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	5.6% 2/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Nervous system disorders Headache	2.5% 3/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	5.6% 2/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Surgical and medical procedures Bypass Graft - Index Leg	1.7% 2/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	5.6% 2/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Respiratory, thoracic and mediastinal disorders Cough	1.7% 2/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	5.6% 2/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Psychiatric disorders Insomnia	1.7% 2/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	5.6% 2/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Skin and subcutaneous tissue disorders Fissure - Index Leg	0.84% 1/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	5.6% 2/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Nervous system disorders Numbness - Index Leg	0.84% 1/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	5.6% 2/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Musculoskeletal and connective tissue disorders Pain - Hip	0.84% 1/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	5.6% 2/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Skin and subcutaneous tissue disorders Pruritis - Index Leg	0.00% 0/119 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.	5.6% 2/36 • All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented. Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.

Additional Information

Hillary Overholser

Zimmer Biomet

Phone: 574-373-2042

Email: hillary.overholser@zimmerbiomet.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place