Trial Outcomes & Findings for A Safety and Efficacy Study of INTEGRA® Dermal Regeneration Template for the Treatment of Diabetic Foot Ulcers (NCT NCT01060670)

NCT ID: NCT01060670

Last Updated: 2016-09-22

Results Overview

100% closure as assessed by the Investigator and confirmed at 2 consecutive treatment phase visits.

Recruitment status

COMPLETED

Study phase

Target enrollment

545 participants

Primary outcome timeframe

16 weeks

Results posted on

2016-09-22

Participant Flow

Participants were recruited based on physician referral at 36 medical centers between March 2010 and November 2013. The first study participant was enrolled in April 2010 and the last study participant was enrolled in November 2013.

Participants participated in a Run-In phase that must last a minimum of 14 days, but may have been extended up to 17 days to allow for scheduling of the randomization visit.

Participant milestones

Participant milestones
Measure	Active Treatment INTEGRA® Dermal Regeneration Template (IDRT) was applied to sharply debrided study ulcer wound bed within an aseptic field. A non-adherent foam dressing, gauze wrap and an offloading/protective device were used in conjunction with the IDRT.	Control Treatment Control Treatment was applied to sharply debrided study ulcer wound bed within an aseptic field. Moist wound therapy consisted of 0.9% sodium chloride gel, applied in conjunction with a non-adherent foam dressing, gauze wrap and an offloading/protective device.
Run In STARTED	0	545
Run In COMPLETED	0	307
Run In NOT COMPLETED	0	238
Treatment Phase STARTED	154	153
Treatment Phase Healed at End of Treatment Phase	79	49
Treatment Phase Did Not Heal by Treatment Visit 17	49	68
Treatment Phase Withdrew From Treatment	26	36
Treatment Phase COMPLETED	128	117
Treatment Phase NOT COMPLETED	26	36
Follow up Phase STARTED	128	117
Follow up Phase Recurrence	14	9
Follow up Phase Withdrew From Follow up Phase	22	35
Follow up Phase COMPLETED	106	82
Follow up Phase NOT COMPLETED	22	35

Reasons for withdrawal

Reasons for withdrawal
Measure	Active Treatment INTEGRA® Dermal Regeneration Template (IDRT) was applied to sharply debrided study ulcer wound bed within an aseptic field. A non-adherent foam dressing, gauze wrap and an offloading/protective device were used in conjunction with the IDRT.	Control Treatment Control Treatment was applied to sharply debrided study ulcer wound bed within an aseptic field. Moist wound therapy consisted of 0.9% sodium chloride gel, applied in conjunction with a non-adherent foam dressing, gauze wrap and an offloading/protective device.
Run In screen failure	0	238

Baseline Characteristics

A Safety and Efficacy Study of INTEGRA® Dermal Regeneration Template for the Treatment of Diabetic Foot Ulcers

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Active Treatment n=154 Participants INTEGRA® Dermal Regeneration Template (IDRT) was applied to sharply debrided study ulcer wound bed within an aseptic field. A non-adherent foam dressing and a gauze wrap and, an offloading/protective device were to be used in conjunction with the IDRT.	Control Treatment n=153 Participants Control Treatment consisted of moist wound therapy and was comprised of 0.9% sodium chloride gel, applied in conjunction with a non-adherent foam dressing and a gauze wrap and, an offloading/protective device	Total n=307 Participants Total of all reporting groups
Age, Continuous	55.8 years n=5 Participants	57.3 years n=7 Participants	56.5 years n=5 Participants
Sex: Female, Male Female	36 Participants n=5 Participants	39 Participants n=7 Participants	75 Participants n=5 Participants
Sex: Female, Male Male	118 Participants n=5 Participants	114 Participants n=7 Participants	232 Participants n=5 Participants
Region of Enrollment United States	152 participants n=5 Participants	151 participants n=7 Participants	303 participants n=5 Participants
Region of Enrollment Netherlands Antilles	2 participants n=5 Participants	2 participants n=7 Participants	4 participants n=5 Participants

PRIMARY outcome

Timeframe: 16 weeks

Population: The results were based on the Investigator assessment and ITT population.

100% closure as assessed by the Investigator and confirmed at 2 consecutive treatment phase visits.

Outcome measures

Outcome measures
Measure	Active Treatment n=154 Participants INTEGRA® Dermal Regeneration Template (IDRT) was applied to sharply debrided study ulcer wound bed within an aseptic field. A non-adherent foam dressing, gauze wrap and an offloading/protective device were used in conjunction with the IDRT.	Control Treatment n=153 Participants Control Treatment was applied to sharply debrided study ulcer wound bed within an aseptic field. Moist wound therapy consisted of 0.9% sodium chloride gel, applied in conjunction with a non-adherent foam dressing, gauze wrap and an offloading/protective device.
Incidence of Complete Wound Closure	79 participants	49 participants

SECONDARY outcome

Timeframe: 16 weeks

Population: ITT Population

Percentage of subjects with complete wound closure of the study ulcer, as assessed by computerized planimetry, during the treatment phase.

Outcome measures

Outcome measures
Measure	Active Treatment n=154 Participants INTEGRA® Dermal Regeneration Template (IDRT) was applied to sharply debrided study ulcer wound bed within an aseptic field. A non-adherent foam dressing, gauze wrap and an offloading/protective device were used in conjunction with the IDRT.	Control Treatment n=153 Participants Control Treatment was applied to sharply debrided study ulcer wound bed within an aseptic field. Moist wound therapy consisted of 0.9% sodium chloride gel, applied in conjunction with a non-adherent foam dressing, gauze wrap and an offloading/protective device.
Incidence of Complete Wound Closure	50 percentage of subjects	31 percentage of subjects

SECONDARY outcome

Timeframe: 16 weeks

Population: ITT Population complete wound healed with analyzable data

Measures the time to complete wound closure as assessed by the Investigator.

Outcome measures

Outcome measures
Measure	Active Treatment n=79 Participants INTEGRA® Dermal Regeneration Template (IDRT) was applied to sharply debrided study ulcer wound bed within an aseptic field. A non-adherent foam dressing, gauze wrap and an offloading/protective device were used in conjunction with the IDRT.	Control Treatment n=49 Participants Control Treatment was applied to sharply debrided study ulcer wound bed within an aseptic field. Moist wound therapy consisted of 0.9% sodium chloride gel, applied in conjunction with a non-adherent foam dressing, gauze wrap and an offloading/protective device.
Time to Complete Wound Closure	52.61 days Standard Deviation 27.22	69.78 days Standard Deviation 31.73

SECONDARY outcome

Timeframe: 16 weeks

Population: ITT population complete wound healed with analyzable data

Time to complete wound closure, as assessed by computerized planimetry.

Outcome measures

Outcome measures
Measure	Active Treatment n=77 Participants INTEGRA® Dermal Regeneration Template (IDRT) was applied to sharply debrided study ulcer wound bed within an aseptic field. A non-adherent foam dressing, gauze wrap and an offloading/protective device were used in conjunction with the IDRT.	Control Treatment n=48 Participants Control Treatment was applied to sharply debrided study ulcer wound bed within an aseptic field. Moist wound therapy consisted of 0.9% sodium chloride gel, applied in conjunction with a non-adherent foam dressing, gauze wrap and an offloading/protective device.
Time to Complete Wound Closure	43 days Interval 15.0 to 123.0	78 days Interval 8.0 to 116.0

SECONDARY outcome

Timeframe: 16 weeks

Population: ITT Population

Rate of wound closure as assessed by computerized planimetry

Outcome measures

Outcome measures
Measure	Active Treatment n=151 Participants INTEGRA® Dermal Regeneration Template (IDRT) was applied to sharply debrided study ulcer wound bed within an aseptic field. A non-adherent foam dressing, gauze wrap and an offloading/protective device were used in conjunction with the IDRT.	Control Treatment n=148 Participants Control Treatment was applied to sharply debrided study ulcer wound bed within an aseptic field. Moist wound therapy consisted of 0.9% sodium chloride gel, applied in conjunction with a non-adherent foam dressing, gauze wrap and an offloading/protective device.
Rate of Wound Closure	7.15 percentage wound closure/week Standard Deviation 8.27	4.81 percentage wound closure/week Standard Deviation 7.34

SECONDARY outcome

Timeframe: 12 weeks

Population: ITT Population complete wound healed

Measures the incidence of ulcer recurrence at the site of the study ulcer during the follow up phase.

Outcome measures

Outcome measures
Measure	Active Treatment n=79 Participants INTEGRA® Dermal Regeneration Template (IDRT) was applied to sharply debrided study ulcer wound bed within an aseptic field. A non-adherent foam dressing, gauze wrap and an offloading/protective device were used in conjunction with the IDRT.	Control Treatment n=49 Participants Control Treatment was applied to sharply debrided study ulcer wound bed within an aseptic field. Moist wound therapy consisted of 0.9% sodium chloride gel, applied in conjunction with a non-adherent foam dressing, gauze wrap and an offloading/protective device.
Incidence of Ulcer Recurrence	15 participants	13 participants

SECONDARY outcome

Timeframe: Baseline and 16 weeks

Population: ITT Population

Short Form Health Survey (SF-36)- Quality of Life Metrics. The SF-36 was utilized and the Physical Function and Bodily Pain subscales were norm-based, with a Mean = 50, SD = 10. Scores could theoretically range from 0 to 100, with higher scores indicating a better health status.

Outcome measures

Outcome measures
Measure	Active Treatment n=154 Participants INTEGRA® Dermal Regeneration Template (IDRT) was applied to sharply debrided study ulcer wound bed within an aseptic field. A non-adherent foam dressing, gauze wrap and an offloading/protective device were used in conjunction with the IDRT.	Control Treatment n=153 Participants Control Treatment was applied to sharply debrided study ulcer wound bed within an aseptic field. Moist wound therapy consisted of 0.9% sodium chloride gel, applied in conjunction with a non-adherent foam dressing, gauze wrap and an offloading/protective device.
Change in Short Form Health Survey (SF-36) Quality of Life Metrics Physical Function	1.28 units on a scale Standard Deviation 11.62	-1.41 units on a scale Standard Deviation 9.22
Change in Short Form Health Survey (SF-36) Quality of Life Metrics Bodily Pain	2.33 units on a scale Standard Deviation 9.42	-.50 units on a scale Standard Deviation 9.82

Adverse Events

Active Treatment

Serious events: 38 serious events

Other events: 0 other events

Deaths: 0 deaths

Control Treatment

Serious events: 55 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Adverse event data not reported

Additional Information

Katie Bush, PhD- Manager, Global Medical Affairs- Tissue Technology

Integra LifeSciences, Inc.

Phone: 617-268-1616

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Investigator shall not publicly disclose any results/information pertaining to the trial until a multi-center publication is released under sponsor's direction; however, if a multi-center publication is not released within 18 months after completion of analysis of all study data from all studies conducted within the multi center trial, Investigator may publish results at their institution as long as they have given sponsor 30 days to review.
Publication restrictions are in place

Restriction type: OTHER

Measure	Active Treatment n=154 participants at risk INTEGRA® Dermal Regeneration Template (IDRT) was applied to sharply debrided study ulcer wound bed within an aseptic field. A non-adherent foam dressing, gauze wrap and an offloading/protective device were used in conjunction with the IDRT.	Control Treatment n=153 participants at risk Control Treatment was applied to sharply debrided study ulcer wound bed within an aseptic field. Moist wound therapy consisted of 0.9% sodium chloride gel, applied in conjunction with a non-adherent foam dressing, gauze wrap and an offloading/protective device.
Cardiac disorders Acute myocardial infarction	0.65% 1/154 • Number of events 1 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.	0.65% 1/153 • Number of events 1 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.
Cardiac disorders atrial fibrillation	0.65% 1/154 • Number of events 1 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.	0.00% 0/153 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.
Cardiac disorders atrial flutter	0.00% 0/154 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.	0.65% 1/153 • Number of events 1 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.
Cardiac disorders cardiac failure	0.65% 1/154 • Number of events 1 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.	0.00% 0/153 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.
Cardiac disorders cardiac failure congestive	0.65% 1/154 • Number of events 1 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.	1.3% 2/153 • Number of events 2 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.
Cardiac disorders cardiac tamponade	0.65% 1/154 • Number of events 1 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.	0.00% 0/153 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.
Cardiac disorders cardiogenic shock	0.00% 0/154 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.	0.65% 1/153 • Number of events 1 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.
Cardiac disorders coronary artery disease	0.00% 0/154 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.	0.65% 1/153 • Number of events 1 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.
Cardiac disorders dyspnoea	0.00% 0/154 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.	0.65% 1/153 • Number of events 1 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.
Eye disorders cataract	0.00% 0/154 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.	0.65% 1/153 • Number of events 1 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.
Gastrointestinal disorders gastritis	0.65% 1/154 • Number of events 1 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.	0.65% 1/153 • Number of events 1 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.
General disorders chest pain	0.65% 1/154 • Number of events 1 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.	0.65% 1/153 • Number of events 1 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.
General disorders condition aggravated	1.3% 2/154 • Number of events 2 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.	3.9% 6/153 • Number of events 6 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.
General disorders multi orgain failure	0.00% 0/154 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.	0.65% 1/153 • Number of events 1 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.
General disorders non cardiac chest pain	0.65% 1/154 • Number of events 1 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.	0.00% 0/153 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.
Hepatobiliary disorders cholecystitis acute	0.65% 1/154 • Number of events 1 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.	0.00% 0/153 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.
Immune system disorders drug hypersensitivity	0.00% 0/154 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.	1.3% 2/153 • Number of events 2 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.
Infections and infestations abcess	0.65% 1/154 • Number of events 1 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.	0.00% 0/153 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.
Infections and infestations abcess limb	0.65% 1/154 • Number of events 1 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.	2.0% 3/153 • Number of events 3 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.
Infections and infestations arthritis bacterial	0.00% 0/154 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.	0.65% 1/153 • Number of events 1 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.
Infections and infestations arthritis infective	0.00% 0/154 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.	0.65% 1/153 • Number of events 1 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.
Infections and infestations bacteraemia	0.65% 1/154 • Number of events 1 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.	0.65% 1/153 • Number of events 1 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.
Infections and infestations cellulitis	4.5% 7/154 • Number of events 7 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.	3.9% 6/153 • Number of events 7 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.
Infections and infestations diabetic foot infection	5.2% 8/154 • Number of events 8 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.	3.9% 6/153 • Number of events 7 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.
Infections and infestations gangrene	0.00% 0/154 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.	2.0% 3/153 • Number of events 3 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.
Infections and infestations infected skin ulcer	0.65% 1/154 • Number of events 1 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.	0.00% 0/153 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.
Infections and infestations localised infection	0.00% 0/154 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.	0.65% 1/153 • Number of events 1 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.
Infections and infestations osteomyelitis	5.2% 8/154 • Number of events 8 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.	9.8% 15/153 • Number of events 15 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.
Infections and infestations perineal abcess	0.65% 1/154 • Number of events 1 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.	0.00% 0/153 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.
Infections and infestations pneumonia	1.9% 3/154 • Number of events 3 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.	2.0% 3/153 • Number of events 3 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.
Infections and infestations sepsis	0.65% 1/154 • Number of events 1 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.	0.65% 1/153 • Number of events 1 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.
Infections and infestations septic shock	0.00% 0/154 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.	0.65% 1/153 • Number of events 1 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.
Infections and infestations soft tissue infection	0.00% 0/154 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.	0.65% 1/153 • Number of events 1 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.
Infections and infestations staphylococcal osteomyelitis	0.00% 0/154 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.	0.65% 1/153 • Number of events 1 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.
Infections and infestations urinary tract infection	0.65% 1/154 • Number of events 3 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.	1.3% 2/153 • Number of events 2 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.
Injury, poisoning and procedural complications ankle fracture	0.65% 1/154 • Number of events 1 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.	0.00% 0/153 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.
Injury, poisoning and procedural complications renal hematoma	0.00% 0/154 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.	0.65% 1/153 • Number of events 1 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.
Metabolism and nutrition disorders diabetic foot	0.65% 1/154 • Number of events 1 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.	0.65% 1/153 • Number of events 1 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.
Metabolism and nutrition disorders diabetic ketoacidosis	0.00% 0/154 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.	2.0% 3/153 • Number of events 5 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.
Metabolism and nutrition disorders hypoglycaemia	0.65% 1/154 • Number of events 1 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.	0.65% 1/153 • Number of events 1 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.
Metabolism and nutrition disorders obesity	0.65% 1/154 • Number of events 1 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.	0.00% 0/153 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.
Musculoskeletal and connective tissue disorders coccydynia	0.00% 0/154 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.	0.65% 1/153 • Number of events 1 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) laryngeal cancer	0.65% 1/154 • Number of events 1 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.	0.00% 0/153 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.
Nervous system disorders convulsion	0.00% 0/154 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.	0.65% 1/153 • Number of events 1 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.
Nervous system disorders loss of consciousness	0.00% 0/154 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.	0.65% 1/153 • Number of events 1 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.
Nervous system disorders syncope	0.00% 0/154 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.	0.65% 1/153 • Number of events 1 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.
Psychiatric disorders mental disorder	0.00% 0/154 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.	0.65% 1/153 • Number of events 1 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.
Renal and urinary disorders renal failure	0.65% 1/154 • Number of events 1 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.	0.00% 0/153 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.
Renal and urinary disorders renal mass	0.00% 0/154 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.	0.65% 1/153 • Number of events 1 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.
Respiratory, thoracic and mediastinal disorders asthma	0.00% 0/154 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.	0.65% 1/153 • Number of events 1 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.
Respiratory, thoracic and mediastinal disorders pulmonary embolism	0.00% 0/154 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.	0.65% 1/153 • Number of events 1 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.
Skin and subcutaneous tissue disorders skin erosion	0.65% 1/154 • Number of events 1 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.	0.00% 0/153 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.
Vascular disorders arterial insufficiency	0.00% 0/154 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.	0.65% 1/153 • Number of events 1 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.
Vascular disorders deep vein thrombosis	0.00% 0/154 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.	0.65% 1/153 • Number of events 1 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.
Vascular disorders extremity necrosis	0.00% 0/154 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.	0.65% 1/153 • Number of events 1 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.
Vascular disorders orthostatic hypotension	0.00% 0/154 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.	0.65% 1/153 • Number of events 1 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.
Vascular disorders peripheral arterial occlusive disease	0.65% 1/154 • Number of events 1 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.	0.00% 0/153 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.
Vascular disorders peripheral vascular disorder	0.00% 0/154 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.	0.65% 1/153 • Number of events 1 • All events starting after the 1st randomized treatment visit through Follow Up visit 3 will be recorded as AEs.