Trial Outcomes & Findings for Low InTensity Exercise Intervention in PAD (NCT NCT02538900)

Last Updated: 2021-11-16

Results Overview

In the six-minute walk, participants walk back and forth along a 100-ft hallway for six minutes after standardized instructions to complete as many laps as possible. Distance covered in six minutes is recorded.

Recruitment status

COMPLETED

Study phase

Target enrollment

305 participants

Primary outcome timeframe

change from baseline to week 52

Results posted on

2021-11-16

Participant Flow

Participant milestones

Participant milestones
Measure	Group 1 Low-intensity, self-paced walking exercise. Home based exercise. Exercise: Participants in one of the exercise intervention groups will attend once weekly sessions at the medical center for the first four weeks of the study (Weeks 1-4, Phase I). During weeks 5-52 (Phase II), they will receive weekly telephone calls from a study coach.	Group 2 Standard high intensity, ischemic pain-inducing walking exercise. Home based exercise. Exercise: Participants in one of the exercise intervention groups will attend once weekly sessions at the medical center for the first four weeks of the study (Weeks 1-4, Phase I). During weeks 5-52 (Phase II), they will receive weekly telephone calls from a study coach.	Group 3 Non-exercising attention control group. Contact with staff at same frequency as exercise groups, but staff deliver information on health not related to exercise. Attention control: Our attention control group controls for the possibility that regular contact with the study team may improve outcomes in participants randomized to the intervention. Participants randomized to the control group will attend weekly one-hour educational sessions at Northwestern University for the first four weeks of the intervention (Phase I). These sessions are on topics of interest to the typical PAD patient and are led by physicians and other health care workers. Topics include Medicare Part D, nutritional supplements, and cancer screening. During Phase II (weeks 5-52), the attention control group will receive weekly telephone calls, lasting 5-15 minutes, with information on a health-related topic.
Overall Study STARTED	116	124	65
Overall Study COMPLETED	96	106	48
Overall Study NOT COMPLETED	20	18	17

Reasons for withdrawal

Reasons for withdrawal
Measure	Group 1 Low-intensity, self-paced walking exercise. Home based exercise. Exercise: Participants in one of the exercise intervention groups will attend once weekly sessions at the medical center for the first four weeks of the study (Weeks 1-4, Phase I). During weeks 5-52 (Phase II), they will receive weekly telephone calls from a study coach.	Group 2 Standard high intensity, ischemic pain-inducing walking exercise. Home based exercise. Exercise: Participants in one of the exercise intervention groups will attend once weekly sessions at the medical center for the first four weeks of the study (Weeks 1-4, Phase I). During weeks 5-52 (Phase II), they will receive weekly telephone calls from a study coach.	Group 3 Non-exercising attention control group. Contact with staff at same frequency as exercise groups, but staff deliver information on health not related to exercise. Attention control: Our attention control group controls for the possibility that regular contact with the study team may improve outcomes in participants randomized to the intervention. Participants randomized to the control group will attend weekly one-hour educational sessions at Northwestern University for the first four weeks of the intervention (Phase I). These sessions are on topics of interest to the typical PAD patient and are led by physicians and other health care workers. Topics include Medicare Part D, nutritional supplements, and cancer screening. During Phase II (weeks 5-52), the attention control group will receive weekly telephone calls, lasting 5-15 minutes, with information on a health-related topic.
Overall Study Death	2	2	2
Overall Study Withdrawal by Subject	18	16	15

Baseline Characteristics

Low InTensity Exercise Intervention in PAD

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Group 1 n=116 Participants Low-intensity, self-paced walking exercise. Home based exercise. Exercise: Participants in one of the exercise intervention groups will attend once weekly sessions at the medical center for the first four weeks of the study (Weeks 1-4, Phase I). During weeks 5-52 (Phase II), they will receive weekly telephone calls from a study coach.	Group 2 n=124 Participants Standard high intensity, ischemic pain-inducing walking exercise. Home based exercise. Exercise: Participants in one of the exercise intervention groups will attend once weekly sessions at the medical center for the first four weeks of the study (Weeks 1-4, Phase I). During weeks 5-52 (Phase II), they will receive weekly telephone calls from a study coach.	Group 3 n=65 Participants Non-exercising attention control group. Contact with staff at same frequency as exercise groups, but staff deliver information on health not related to exercise. Attention control: Our attention control group controls for the possibility that regular contact with the study team may improve outcomes in participants randomized to the intervention. Participants randomized to the control group will attend weekly one-hour educational sessions at Northwestern University for the first four weeks of the intervention (Phase I). These sessions are on topics of interest to the typical PAD patient and are led by physicians and other health care workers. Topics include Medicare Part D, nutritional supplements, and cancer screening. During Phase II (weeks 5-52), the attention control group will receive weekly telephone calls, lasting 5-15 minutes, with information on a health-related topic.	Total n=305 Participants Total of all reporting groups
Age, Continuous	69.8 years STANDARD_DEVIATION 10.1 • n=5 Participants	68.8 years STANDARD_DEVIATION 8.7 • n=7 Participants	69.5 years STANDARD_DEVIATION 10.1 • n=5 Participants	69.3 years STANDARD_DEVIATION 9.5 • n=4 Participants
Sex: Female, Male Female	54 Participants n=5 Participants	60 Participants n=7 Participants	32 Participants n=5 Participants	146 Participants n=4 Participants
Sex: Female, Male Male	62 Participants n=5 Participants	64 Participants n=7 Participants	33 Participants n=5 Participants	159 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Asian	4 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	6 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	65 Participants n=5 Participants	81 Participants n=7 Participants	35 Participants n=5 Participants	181 Participants n=4 Participants
Race (NIH/OMB) White	45 Participants n=5 Participants	41 Participants n=7 Participants	28 Participants n=5 Participants	114 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants
Region of Enrollment United States	116 participants n=5 Participants	124 participants n=7 Participants	65 participants n=5 Participants	305 participants n=4 Participants
Ankle-brachial index	0.66 ratio STANDARD_DEVIATION 0.17 • n=5 Participants	0.67 ratio STANDARD_DEVIATION 0.15 • n=7 Participants	0.67 ratio STANDARD_DEVIATION 0.15 • n=5 Participants	0.66 ratio STANDARD_DEVIATION 0.16 • n=4 Participants
Body mass index	30.3 kg/m^2 STANDARD_DEVIATION 6.7 • n=5 Participants	31.1 kg/m^2 STANDARD_DEVIATION 7.3 • n=7 Participants	30.8 kg/m^2 STANDARD_DEVIATION 7.3 • n=5 Participants	30.7 kg/m^2 STANDARD_DEVIATION 7.1 • n=4 Participants
Six-min walk distance	326 meters STANDARD_DEVIATION 99 • n=5 Participants	329 meters STANDARD_DEVIATION 101 • n=7 Participants	328 meters STANDARD_DEVIATION 87 • n=5 Participants	328 meters STANDARD_DEVIATION 97 • n=4 Participants

PRIMARY outcome

Timeframe: change from baseline to week 52

Outcome measures

Outcome measures
Measure	Group 1 n=116 Participants Low-intensity, self-paced walking exercise. Home based exercise. Exercise: Participants in one of the exercise intervention groups will attend once weekly sessions at the medical center for the first four weeks of the study (Weeks 1-4, Phase I). During weeks 5-52 (Phase II), they will receive weekly telephone calls from a study coach.	Group 2 n=124 Participants Standard high intensity, ischemic pain-inducing walking exercise. Home based exercise. Exercise: Participants in one of the exercise intervention groups will attend once weekly sessions at the medical center for the first four weeks of the study (Weeks 1-4, Phase I). During weeks 5-52 (Phase II), they will receive weekly telephone calls from a study coach.	Group 3 n=65 Participants Non-exercising attention control group. Contact with staff at same frequency as exercise groups, but staff deliver information on health not related to exercise. Attention control: Our attention control group controls for the possibility that regular contact with the study team may improve outcomes in participants randomized to the intervention. Participants randomized to the control group will attend weekly one-hour educational sessions at Northwestern University for the first four weeks of the intervention (Phase I). These sessions are on topics of interest to the typical PAD patient and are led by physicians and other health care workers. Topics include Medicare Part D, nutritional supplements, and cancer screening. During Phase II (weeks 5-52), the attention control group will receive weekly telephone calls, lasting 5-15 minutes, with information on a health-related topic.
Six-minute Walk Distance	-6.4 meters Interval -21.5 to 8.8	34.5 meters Interval 20.1 to 48.9	-15.1 meters Interval -35.8 to 5.7

SECONDARY outcome

Timeframe: change from baseline to week 26

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: change from baseline to week 52

In the treadmill walking test, participants walk on either a gardner or modified gardner protocol until they stop the test. Time walked is recorded

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Change from baseline to week 52

ActiGraph measured physical activity

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: change from baseline to week 52

The WIQ is a well validated questionnaire that measures patient-reported walking limitations in distance and speed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: change from baseline to week 52

The SF-36 physical functioning score will be used to measure quality of life.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: from baseline to week 52

Adherence is defined as the proportion achieving at least 80% of the prescribed exercise frequency and duration during the final month of the intervention.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: change from baseline to week 52

Muscle tissue will be collected at baseline and follow up to measures Change in muscle biopsy measures of mitochondrial oxidative metabolism and oxidative stress.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: At 52 week follow up

We will use qualitative methods to explore participants' perceptions of the exercise interventions in the high and low-intensity exercise groups, respectively.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 26 week follow-up.

ActiGraph

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 26 week follow-up

The WIQ is a well validated questionnaire that measures patient-reported walking limitations in distance and speed.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 26 weeks

SF-36 physical functioning score.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 26 weeks.

Adherence is defined as the proportion achieving at least 80% of the prescribed exercise frequency and duration during the final month of the intervention.

Outcome measures

Outcome data not reported

Adverse Events

Group 1

Serious events: 43 serious events

Other events: 34 other events

Deaths: 2 deaths

Group 2

Serious events: 40 serious events

Other events: 42 other events

Deaths: 2 deaths

Group 3

Serious events: 19 serious events

Other events: 29 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Group 1 n=116 participants at risk Low-intensity, self-paced walking exercise. Home based exercise. Exercise: Participants in one of the exercise intervention groups will attend once weekly sessions at the medical center for the first four weeks of the study (Weeks 1-4, Phase I). During weeks 5-52 (Phase II), they will receive weekly telephone calls from a study coach.	Group 2 n=124 participants at risk Standard high intensity, ischemic pain-inducing walking exercise. Home based exercise. Exercise: Participants in one of the exercise intervention groups will attend once weekly sessions at the medical center for the first four weeks of the study (Weeks 1-4, Phase I). During weeks 5-52 (Phase II), they will receive weekly telephone calls from a study coach.	Group 3 n=65 participants at risk Non-exercising attention control group. Contact with staff at same frequency as exercise groups, but staff deliver information on health not related to exercise. Attention control: Our attention control group controls for the possibility that regular contact with the study team may improve outcomes in participants randomized to the intervention. Participants randomized to the control group will attend weekly one-hour educational sessions at Northwestern University for the first four weeks of the intervention (Phase I). These sessions are on topics of interest to the typical PAD patient and are led by physicians and other health care workers. Topics include Medicare Part D, nutritional supplements, and cancer screening. During Phase II (weeks 5-52), the attention control group will receive weekly telephone calls, lasting 5-15 minutes, with information on a health-related topic.
General disorders New or increased chest discomfort during activity or exercise	7.8% 9/116 • Number of events 11 • Adverse event data were collected monthly through out the 12-month intervention period.	12.9% 16/124 • Number of events 23 • Adverse event data were collected monthly through out the 12-month intervention period.	12.3% 8/65 • Number of events 14 • Adverse event data were collected monthly through out the 12-month intervention period.
General disorders New or increased shortness of breath during activity or exercise	11.2% 13/116 • Number of events 21 • Adverse event data were collected monthly through out the 12-month intervention period.	19.4% 24/124 • Number of events 38 • Adverse event data were collected monthly through out the 12-month intervention period.	29.2% 19/65 • Number of events 30 • Adverse event data were collected monthly through out the 12-month intervention period.
General disorders New or increased dizziness or generalized weakness during activity or exercise	19.8% 23/116 • Number of events 25 • Adverse event data were collected monthly through out the 12-month intervention period.	16.9% 21/124 • Number of events 28 • Adverse event data were collected monthly through out the 12-month intervention period.	33.8% 22/65 • Number of events 42 • Adverse event data were collected monthly through out the 12-month intervention period.

Additional Information

Mary McDermott MD

Northwestern University

Phone: 312-503-6419

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Group 1 n=116 participants at risk Low-intensity, self-paced walking exercise. Home based exercise. Exercise: Participants in one of the exercise intervention groups will attend once weekly sessions at the medical center for the first four weeks of the study (Weeks 1-4, Phase I). During weeks 5-52 (Phase II), they will receive weekly telephone calls from a study coach.	Group 2 n=124 participants at risk Standard high intensity, ischemic pain-inducing walking exercise. Home based exercise. Exercise: Participants in one of the exercise intervention groups will attend once weekly sessions at the medical center for the first four weeks of the study (Weeks 1-4, Phase I). During weeks 5-52 (Phase II), they will receive weekly telephone calls from a study coach.	Group 3 n=65 participants at risk Non-exercising attention control group. Contact with staff at same frequency as exercise groups, but staff deliver information on health not related to exercise. Attention control: Our attention control group controls for the possibility that regular contact with the study team may improve outcomes in participants randomized to the intervention. Participants randomized to the control group will attend weekly one-hour educational sessions at Northwestern University for the first four weeks of the intervention (Phase I). These sessions are on topics of interest to the typical PAD patient and are led by physicians and other health care workers. Topics include Medicare Part D, nutritional supplements, and cancer screening. During Phase II (weeks 5-52), the attention control group will receive weekly telephone calls, lasting 5-15 minutes, with information on a health-related topic.
General disorders Complication from angiogram	0.00% 0/116 • Adverse event data were collected monthly through out the 12-month intervention period.	0.81% 1/124 • Number of events 1 • Adverse event data were collected monthly through out the 12-month intervention period.	0.00% 0/65 • Adverse event data were collected monthly through out the 12-month intervention period.
Cardiac disorders Lower extremity revascularization	6.9% 8/116 • Number of events 8 • Adverse event data were collected monthly through out the 12-month intervention period.	7.3% 9/124 • Number of events 9 • Adverse event data were collected monthly through out the 12-month intervention period.	3.1% 2/65 • Number of events 2 • Adverse event data were collected monthly through out the 12-month intervention period.
Infections and infestations Infection	5.2% 6/116 • Number of events 6 • Adverse event data were collected monthly through out the 12-month intervention period.	8.9% 11/124 • Number of events 11 • Adverse event data were collected monthly through out the 12-month intervention period.	1.5% 1/65 • Number of events 1 • Adverse event data were collected monthly through out the 12-month intervention period.
General disorders Chest pain	4.3% 5/116 • Number of events 5 • Adverse event data were collected monthly through out the 12-month intervention period.	3.2% 4/124 • Number of events 4 • Adverse event data were collected monthly through out the 12-month intervention period.	7.7% 5/65 • Number of events 5 • Adverse event data were collected monthly through out the 12-month intervention period.
Cardiac disorders Ischemic heart disease	3.4% 4/116 • Number of events 4 • Adverse event data were collected monthly through out the 12-month intervention period.	3.2% 4/124 • Number of events 4 • Adverse event data were collected monthly through out the 12-month intervention period.	0.00% 0/65 • Adverse event data were collected monthly through out the 12-month intervention period.
General disorders Abdominal problem	2.6% 3/116 • Number of events 3 • Adverse event data were collected monthly through out the 12-month intervention period.	4.0% 5/124 • Number of events 5 • Adverse event data were collected monthly through out the 12-month intervention period.	0.00% 0/65 • Adverse event data were collected monthly through out the 12-month intervention period.
General disorders Diabetes	2.6% 3/116 • Number of events 3 • Adverse event data were collected monthly through out the 12-month intervention period.	1.6% 2/124 • Number of events 2 • Adverse event data were collected monthly through out the 12-month intervention period.	3.1% 2/65 • Number of events 2 • Adverse event data were collected monthly through out the 12-month intervention period.
General disorders GI bleed	0.86% 1/116 • Number of events 1 • Adverse event data were collected monthly through out the 12-month intervention period.	3.2% 4/124 • Number of events 4 • Adverse event data were collected monthly through out the 12-month intervention period.	3.1% 2/65 • Number of events 2 • Adverse event data were collected monthly through out the 12-month intervention period.
Vascular disorders Critical limb ischemia	1.7% 2/116 • Number of events 2 • Adverse event data were collected monthly through out the 12-month intervention period.	3.2% 4/124 • Number of events 4 • Adverse event data were collected monthly through out the 12-month intervention period.	0.00% 0/65 • Adverse event data were collected monthly through out the 12-month intervention period.
General disorders Fall or fracture	2.6% 3/116 • Number of events 3 • Adverse event data were collected monthly through out the 12-month intervention period.	0.81% 1/124 • Number of events 1 • Adverse event data were collected monthly through out the 12-month intervention period.	3.1% 2/65 • Number of events 2 • Adverse event data were collected monthly through out the 12-month intervention period.
General disorders Pulmonary event	4.3% 5/116 • Number of events 5 • Adverse event data were collected monthly through out the 12-month intervention period.	0.00% 0/124 • Adverse event data were collected monthly through out the 12-month intervention period.	1.5% 1/65 • Number of events 1 • Adverse event data were collected monthly through out the 12-month intervention period.
Cardiac disorders Stroke or cerebral hemorrhage	1.7% 2/116 • Number of events 2 • Adverse event data were collected monthly through out the 12-month intervention period.	2.4% 3/124 • Number of events 3 • Adverse event data were collected monthly through out the 12-month intervention period.	1.5% 1/65 • Number of events 1 • Adverse event data were collected monthly through out the 12-month intervention period.
General disorders Elective surgery	2.6% 3/116 • Number of events 3 • Adverse event data were collected monthly through out the 12-month intervention period.	0.81% 1/124 • Number of events 1 • Adverse event data were collected monthly through out the 12-month intervention period.	1.5% 1/65 • Number of events 1 • Adverse event data were collected monthly through out the 12-month intervention period.
General disorders Syncope	0.86% 1/116 • Number of events 1 • Adverse event data were collected monthly through out the 12-month intervention period.	1.6% 2/124 • Number of events 2 • Adverse event data were collected monthly through out the 12-month intervention period.	3.1% 2/65 • Number of events 2 • Adverse event data were collected monthly through out the 12-month intervention period.
General disorders Arrhythmia	1.7% 2/116 • Number of events 2 • Adverse event data were collected monthly through out the 12-month intervention period.	1.6% 2/124 • Number of events 2 • Adverse event data were collected monthly through out the 12-month intervention period.	0.00% 0/65 • Adverse event data were collected monthly through out the 12-month intervention period.
General disorders Coronary revascularization	2.6% 3/116 • Number of events 3 • Adverse event data were collected monthly through out the 12-month intervention period.	0.81% 1/124 • Number of events 1 • Adverse event data were collected monthly through out the 12-month intervention period.	0.00% 0/65 • Adverse event data were collected monthly through out the 12-month intervention period.
Cardiac disorders Heart failure	0.00% 0/116 • Adverse event data were collected monthly through out the 12-month intervention period.	3.2% 4/124 • Number of events 4 • Adverse event data were collected monthly through out the 12-month intervention period.	0.00% 0/65 • Adverse event data were collected monthly through out the 12-month intervention period.
General disorders Lightheaded	1.7% 2/116 • Number of events 2 • Adverse event data were collected monthly through out the 12-month intervention period.	0.81% 1/124 • Number of events 1 • Adverse event data were collected monthly through out the 12-month intervention period.	1.5% 1/65 • Number of events 1 • Adverse event data were collected monthly through out the 12-month intervention period.
General disorders Venous thromboembolism	1.7% 2/116 • Number of events 2 • Adverse event data were collected monthly through out the 12-month intervention period.	1.6% 2/124 • Number of events 2 • Adverse event data were collected monthly through out the 12-month intervention period.	0.00% 0/65 • Adverse event data were collected monthly through out the 12-month intervention period.
Cardiac disorders Carotid revascularization	2.6% 3/116 • Number of events 3 • Adverse event data were collected monthly through out the 12-month intervention period.	0.00% 0/124 • Adverse event data were collected monthly through out the 12-month intervention period.	0.00% 0/65 • Adverse event data were collected monthly through out the 12-month intervention period.
General disorders Headache	2.6% 3/116 • Number of events 3 • Adverse event data were collected monthly through out the 12-month intervention period.	0.00% 0/124 • Adverse event data were collected monthly through out the 12-month intervention period.	0.00% 0/65 • Adverse event data were collected monthly through out the 12-month intervention period.
General disorders Hypertension	0.86% 1/116 • Number of events 1 • Adverse event data were collected monthly through out the 12-month intervention period.	0.81% 1/124 • Number of events 1 • Adverse event data were collected monthly through out the 12-month intervention period.	0.00% 0/65 • Adverse event data were collected monthly through out the 12-month intervention period.
General disorders Abdominal infection	0.00% 0/116 • Adverse event data were collected monthly through out the 12-month intervention period.	0.81% 1/124 • Number of events 1 • Adverse event data were collected monthly through out the 12-month intervention period.	0.00% 0/65 • Adverse event data were collected monthly through out the 12-month intervention period.
General disorders Acute renal failure	1.7% 2/116 • Number of events 2 • Adverse event data were collected monthly through out the 12-month intervention period.	0.00% 0/124 • Adverse event data were collected monthly through out the 12-month intervention period.	0.00% 0/65 • Adverse event data were collected monthly through out the 12-month intervention period.
General disorders Bronchitis	0.00% 0/116 • Adverse event data were collected monthly through out the 12-month intervention period.	1.6% 2/124 • Number of events 2 • Adverse event data were collected monthly through out the 12-month intervention period.	0.00% 0/65 • Adverse event data were collected monthly through out the 12-month intervention period.
General disorders Cancer	0.86% 1/116 • Number of events 1 • Adverse event data were collected monthly through out the 12-month intervention period.	0.00% 0/124 • Adverse event data were collected monthly through out the 12-month intervention period.	0.00% 0/65 • Adverse event data were collected monthly through out the 12-month intervention period.
General disorders Colitis	0.00% 0/116 • Adverse event data were collected monthly through out the 12-month intervention period.	0.00% 0/124 • Adverse event data were collected monthly through out the 12-month intervention period.	3.1% 2/65 • Number of events 2 • Adverse event data were collected monthly through out the 12-month intervention period.
General disorders Dehydration	0.86% 1/116 • Number of events 1 • Adverse event data were collected monthly through out the 12-month intervention period.	0.81% 1/124 • Number of events 1 • Adverse event data were collected monthly through out the 12-month intervention period.	0.00% 0/65 • Adverse event data were collected monthly through out the 12-month intervention period.
General disorders Esophageal problem	0.86% 1/116 • Number of events 1 • Adverse event data were collected monthly through out the 12-month intervention period.	0.00% 0/124 • Adverse event data were collected monthly through out the 12-month intervention period.	1.5% 1/65 • Number of events 1 • Adverse event data were collected monthly through out the 12-month intervention period.
General disorders PAD	0.00% 0/116 • Adverse event data were collected monthly through out the 12-month intervention period.	1.6% 2/124 • Number of events 2 • Adverse event data were collected monthly through out the 12-month intervention period.	0.00% 0/65 • Adverse event data were collected monthly through out the 12-month intervention period.
General disorders Angina	0.00% 0/116 • Adverse event data were collected monthly through out the 12-month intervention period.	0.81% 1/124 • Number of events 1 • Adverse event data were collected monthly through out the 12-month intervention period.	0.00% 0/65 • Adverse event data were collected monthly through out the 12-month intervention period.
General disorders Bowel obstruction	0.86% 1/116 • Number of events 1 • Adverse event data were collected monthly through out the 12-month intervention period.	0.00% 0/124 • Adverse event data were collected monthly through out the 12-month intervention period.	0.00% 0/65 • Adverse event data were collected monthly through out the 12-month intervention period.
General disorders Complication from medical procedure	0.00% 0/116 • Adverse event data were collected monthly through out the 12-month intervention period.	0.81% 1/124 • Number of events 1 • Adverse event data were collected monthly through out the 12-month intervention period.	0.00% 0/65 • Adverse event data were collected monthly through out the 12-month intervention period.
General disorders Congestive heart failure	0.00% 0/116 • Adverse event data were collected monthly through out the 12-month intervention period.	0.81% 1/124 • Number of events 1 • Adverse event data were collected monthly through out the 12-month intervention period.	0.00% 0/65 • Adverse event data were collected monthly through out the 12-month intervention period.
General disorders Diagnostic testing	0.00% 0/116 • Adverse event data were collected monthly through out the 12-month intervention period.	0.81% 1/124 • Number of events 1 • Adverse event data were collected monthly through out the 12-month intervention period.	0.00% 0/65 • Adverse event data were collected monthly through out the 12-month intervention period.
General disorders Electrolyte problem	0.00% 0/116 • Adverse event data were collected monthly through out the 12-month intervention period.	0.81% 1/124 • Number of events 1 • Adverse event data were collected monthly through out the 12-month intervention period.	0.00% 0/65 • Adverse event data were collected monthly through out the 12-month intervention period.
General disorders Medication side effect	0.00% 0/116 • Adverse event data were collected monthly through out the 12-month intervention period.	0.00% 0/124 • Adverse event data were collected monthly through out the 12-month intervention period.	1.5% 1/65 • Number of events 1 • Adverse event data were collected monthly through out the 12-month intervention period.
General disorders Mental status	0.00% 0/116 • Adverse event data were collected monthly through out the 12-month intervention period.	0.81% 1/124 • Number of events 1 • Adverse event data were collected monthly through out the 12-month intervention period.	0.00% 0/65 • Adverse event data were collected monthly through out the 12-month intervention period.
General disorders Musculoskeletal	0.86% 1/116 • Number of events 1 • Adverse event data were collected monthly through out the 12-month intervention period.	0.00% 0/124 • Adverse event data were collected monthly through out the 12-month intervention period.	0.00% 0/65 • Adverse event data were collected monthly through out the 12-month intervention period.
General disorders Neurologic problem	0.86% 1/116 • Number of events 1 • Adverse event data were collected monthly through out the 12-month intervention period.	0.00% 0/124 • Adverse event data were collected monthly through out the 12-month intervention period.	0.00% 0/65 • Adverse event data were collected monthly through out the 12-month intervention period.
General disorders Pleural effusions	0.86% 1/116 • Number of events 1 • Adverse event data were collected monthly through out the 12-month intervention period.	0.00% 0/124 • Adverse event data were collected monthly through out the 12-month intervention period.	0.00% 0/65 • Adverse event data were collected monthly through out the 12-month intervention period.
General disorders Psychiatric	0.86% 1/116 • Number of events 1 • Adverse event data were collected monthly through out the 12-month intervention period.	0.00% 0/124 • Adverse event data were collected monthly through out the 12-month intervention period.	0.00% 0/65 • Adverse event data were collected monthly through out the 12-month intervention period.
General disorders Testicular problem	0.00% 0/116 • Adverse event data were collected monthly through out the 12-month intervention period.	0.81% 1/124 • Number of events 1 • Adverse event data were collected monthly through out the 12-month intervention period.	1.5% 1/65 • Number of events 1 • Adverse event data were collected monthly through out the 12-month intervention period.
General disorders Ulcer	0.00% 0/116 • Adverse event data were collected monthly through out the 12-month intervention period.	0.00% 0/124 • Adverse event data were collected monthly through out the 12-month intervention period.	1.5% 1/65 • Number of events 1 • Adverse event data were collected monthly through out the 12-month intervention period.
General disorders Weight loss	0.00% 0/116 • Adverse event data were collected monthly through out the 12-month intervention period.	0.00% 0/124 • Adverse event data were collected monthly through out the 12-month intervention period.	1.5% 1/65 • Number of events 1 • Adverse event data were collected monthly through out the 12-month intervention period.