Community Walking Exercise for Patients With Peripheral Artery Disease

The investigators will test the hypothesis that PAD patients randomized to the exercise program in the community setting incorporating TMC+ will improve walking ability compared with patients who receive the standard of care (exercise advice). Secondary hypotheses include a significant improvement in patient-reported outcomes, an improvement in functional ability or a significant increase in volume of physical activity for patients who complete community-based walking exercise when compared with patients receiving the standard of care. Exploratory hypotheses include a significant improvement in PWT for 1) patients receiving a combination of lower extremity endovascular therapy (ET) and community-based walking exercise or 2) open peripheral intervention and community-based walking exercise compared to patients who do not receive endovascular therapy or open intervention and receive only the standard of care.

Inclusion criteria

• Men and women diagnosed with atherosclerotic PAD
• ≥40 years of age
• An abnormal ankle-brachial index (ABI) of ≤.90
• For patients with an ABI >.90 and <1.00, a post-exercise ABI drop of 15% or more compared to the resting ABI
• Patients receiving lower extremity ET or peripheral open intervention
• Patients not receiving lower extremity ET or peripheral open intervention but present with stable claudication and an abnormal ABI

Exclusion criteria

• Lower extremity amputation(s), including a toe amputation, which interfere (s) with walking on the treadmill
• Individuals with critical limb ischemia defined by ischemic rest pain or ischemic ulcers/gangrene on the lower extremities
• PAD of non-atherosclerotic nature (e.g., fibromuscular dysplasia, irradiation, endofibrosis)
• Coronary artery bypass grafts or major surgical procedures within 6 months prior to screening
• Individuals whose walking exercise is primarily limited by symptoms of chronic obstructive pulmonary disease, angina, or heart failure
• Individuals who are unable to walk on the treadmill at a speed of at least 2 mph for at least 1 minute
• Individuals who have had a myocardial infarction within 3 months prior to screening
• Individuals who demonstrate symptoms consistent with acute coronary syndrome
• Individuals who exhibit ischemia as documented on the 12-lead electrocardiogram including horizontal or down-sloping ST-segment depression ≥0.5 mm at rest and >1 mm with exercise in 2 contiguous leads, relative to the PR-segment (ST-segment measured 0.08 seconds after the J point, ST-segment elevation ≥1 mm)
• Individuals who have had a transient ischemic attack or stroke 3 months prior to screening
• Individuals with left bundle branch block or sustained ventricular tachycardia (>30 sec) during screening
• Individuals with uncontrolled hypertension (≥180 systolic or ≥100 diastolic resting blood pressure) during screening
• Treatment with pentoxifylline or cilostazol for the treatment of claudication 4 weeks prior to screening; Patients can be reconsidered for study inclusion following a 1 month washout period from these medications
• Electrolyte abnormalities (e.g., potassium <3.3 mmol∙Lˉ1 )
• Pregnancy, fertility without protection against pregnancy (for women of childbearing potential, a serum pregnancy test will be performed at screening)
• Incarcerated individuals
• Individuals acutely impaired by alcohol or other illicit drugs
• Poorly controlled diabetes defined as glycated hemoglobin >12%
• Severely anemic patients (Hgb <11 g∙dLˉ1 for women and <10 g∙dLˉ1 for men)
• For patients who have not received peripheral revascularization, an ABI of >0.90
• For patients with equivocal resting ABIs (0.91-0.99), a drop of <15% in the post-exercise ABI
• For individuals with non-compressible vessels (ABI >1.39) who have a toe- brachial index (TBI) >0.70
• Inability to speak English
• Other clinically significant disease that is, in the opinion of the study team, not stabilized or may otherwise confound the results of the study