Overview
The INTERCEDE randomized trial will establish whether six-months of intermittent pneumatic compression combined with walking exercise improves walking endurance at six-month follow-up, compared to walking exercise + sham compression therapy, in people with lower extremity peripheral artery disease (PAD). The INTERCEDE trial will also determine whether intermittent pneumatic compression therapy improves walking endurance at 6-month follow-up, compared to a sham compression therapy. The trial will also determine whether benefits of intermittent pneumatic compression persist after intermittent pneumatic compression treatment is completed.
Description
Walking exercise is first-line therapy for PAD. However, many PAD patients are unable or unwilling to exercise. Therefore, in people with PAD, the investigators will determine whether intermittent pneumatic compression augments the benefits of exercise and whether intermittent pneumatic compression alone improves walking performance compared to sham control. The investigators will conduct a randomized trial (2 x 2 factorial design) of 230 PAD participants randomized to one of four groups: Group A: intermittent pneumatic compression + exercise; Group B: intermittent pneumatic compression+ "no exercise" control; Group C: sham control + exercise; and Group D: sham control + "no exercise" control. The intermittent pneumatic compression and sham interventions will be delivered for six months. The primary outcome is change in six-minute walk distance at 6-month follow-up. In secondary aims, the investigators will determine whether the benefits of intermittent pneumatic compression persist even after intermittent pneumatic compression is discontinued and delineate mechanisms by which intermittent pneumatic compression affects walking performance, by measuring changes in MRI-measured calf muscle perfusion and physical activity. The investigators will determine whether intermittent pneumatic compression improves systemic endothelial function, by measuring changes in brachial artery flow-mediated dilation (FMD).
Eligibility
Inclusion Criteria:
All participants will have PAD. PAD will be defined as follows: first, an ankle-brachial
index (ABI) < or = 0.90 at the baseline study visit is an inclusion criterion for PAD.
Second, potential participants with an ABI >0.90 who have vascular laboratory evidence of
PAD. Vascular laboratory evidence consists of objective evidence of PAD, including toe
brachial index (TBI) < or = 0.70, Duplex measure showing 70% stenosis or greater, or ABI
values < 0.90. Abnormal waveforms or pulse volume recordings alone from a non-invasive
vascular laboratory test will not be sufficient for enrollment. Third, potential
participants with an ABI >0.90 who have angiographic evidence of PAD consisting of a
stenosis of 70% or greater in a lower extremity artery.
Exclusion Criteria:
1. Above- or below-knee amputation.
2. Critical limb ischemia or ABI < 0.30 in the setting of ischemic symptoms at rest or
physical examination findings consistent with critical limb ischemia. Some potential
participants with symptoms or signs of critical limb ischemia may be excluded at the
principal investigator's discretion if the ABI is 0.30 or higher.
3. Wheelchair-bound.
4. Current foot ulcer on bottom of foot.
5. Walking is primarily limited by a symptom other than PAD.
6. Failure to successfully complete the study run-in.
7. Major surgery, revascularization, or orthopedic surgery in the past 3 months or
planned in the next 12 months.
8. Major medical illness including Parkinson's Disease, lung disease requiring oxygen,
cancer requiring treatment in the previous two years, or life-threatening illness with
a life expectancy of less than six months. Participants who only use oxygen at night
will be potentially eligible. [NOTE: potential participants treated for cancer in the
past two years may still qualify if they have had treatment for early stage cancer in
the past two years and the prognosis is excellent. Potential participants treated for
basal cell or squamous cell skin cancer will not be excluded.]
9. Already exercising at a level consistent with exercise intervention. Current or recent
participation in exercise rehabilitation (within the past three months).
10. Recently diagnosed (within the past three months) with acute lower extremity deep
venous thrombosis, pulmonary embolism, or severe heart failure (i.e. New York Heart
Association (NYHA) Class III or IV).
11. Mini-Mental Status Examination (MMSE) score <23 or dementia.
12. Participation in or completion of a clinical trial in the previous three months.
13. Non-English speaking.
14. Increase in angina in the past month, angina at rest, or abnormal baseline treadmill
stress test. Potential participants may become eligible after an abnormal baseline
treadmill stress test if they have evidence of an absence of coronary ischemia based
on testing (such as a stress test with imaging or a coronary angiogram) from a test
performed with their own physician and if they do not have symptoms of unstable
angina. The evidence of absent coronary ischemia, based on an imaging stress test or
coronary angiogram, must have been performed within the previous year.
15. Ongoing infection of the toes, foot, or lower extremity.
16. Potential participants who started on cilostazol within the last three months. They
may be evaluated for eligibility once three months have passed since beginning
cilostazol.
17. Significant peripheral edema, defined as 3+ or greater edema severity, as determined
by the principal investigator.
18. BMI >45 kg/M2
19. Significant visual impairment that interferes with walking.
20. In addition to the above criteria, investigator discretion will be used to determine
if the trial is unsafe or not a good fit for the potential participant.