Claudication: Exercise Versus Endoluminal Revascularization (CLEVER)

• Status: Unknown status
• Trial end date: 2013-07-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to compare the effectiveness of aortic stent surgery versus exercise therapy in individuals with aortoiliac insufficiency.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Joselyn Cerezo, MD
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI)
• Treatments: Cilostazol

Criteria

Inclusion Criteria:

• Subject has symptoms suggestive of intermittent claudication, such as exercise-induced pain, cramps, fatigue, or other equivalent discomfort, involving large muscle groups of the leg(s) (calf, thigh, buttocks), relieved by rest

• Claudication score consistent with "Rose", "atypical", or "noncalf" claudication by San Diego Claudication Questionnaire

• Positive noninvasive evaluation for significant aortoiliac PAD on the most symptomatic side(s) (bilaterally if symptoms are equal):

• Contrast Arteriography: Contrast arteriogram showing at least 50% stenosis in the aorta, common iliac artery, or external iliac artery, OR

• CTA or MRA: Ankle-brachial index less than or equal to 0.9 (or abnormal ankle PVR waveform at ankle if arteries are incompressible*) with at least 60% stenosis in the aorta, common iliac artery, external iliac artery, accompanied by a biphasic or monophasic Doppler wave form at the common femoral artery (loss of early diastolic flow reversal or loss of forward flow during diastole), OR

• Duplex Ultrasound: Ankle-brachial index less than or equal to 0.9 (or abnormal ankle PVR waveform at ankle if arteries are incompressible*) with occlusion or focal doubling of peak systolic velocity in the aorta, common iliac artery, or external iliac artery, accompanied by a biphasic or monophasic Doppler wave form at the common femoral artery (loss of early diastolic flow reversal or loss of forward flow during diastole), OR

• Vascular Noninvasive Physiologic Tests: Ankle-brachial index less than or equal to 0.9 (or abnormal ankle PVR waveform at ankle if arteries are incompressible*) with resting thigh-brachial index (thigh-BI) less than 1.1, and common femoral artery Doppler systolic acceleration time greater than 140 msec [these tests may be ordered for study screening].

• Abnormal PVR waveform must lack augmentation at the ankle, have a delayed, rounded systolic peak, and straight or convex downslope, and must be reviewed by the core lab.

Note: MRA/CTA, and contrast arteriogram images images must be submitted to the Clinical Coordinating Center and Doppler waveform tracings to the Noninvasive Test Committee for over read pre- or post-randomization

• Highest ankle pressure reduced by at least 25 mm Hg after exercise compared to resting pressure (or loss of previously present Doppler signal for both the posterior tibial and anterior tibial arteries immediately after exercise if arteries were incompressible) Note: The highest ankle pressure result is determined by using the higher result of either the dorsalis pedis or posterior tibial artery measurement.

• Subject has moderate to severe claudication symptoms, defined as less than 11 minutes MWD at baseline (initial) Gardner treadmill test

Exclusion Criteria:

• Presence of critical limb ischemia (Rutherford Grade II or III59 PAD, defined as pain at rest, ischemic ulceration, gangrene) or acute limb ischemia (pain, pallor, pulselessness, paresthesias, paralysis) in either leg

• Common femoral artery (CFA) occlusion or greater than or equal to 50% stenosis by angiography, MRA, CTA, or duplex ultrasound or doubling of systolic velocity in the ipsilateral common femoral artery by duplex ultrasound, or 50% diameter stenosis by visual estimate in the CFA by angiography, MRA, or CTA, (inadequate outflow for iliac stent intervention), if available pre-randomization

• Known total aortoiliac occlusion from the renal arteries to the inguinal ligaments (all other occlusions, including aortic occlusion, ARE eligible)

• Participant has bilateral claudication symptoms and the limb that is more symptomatic does not show evidence of aortoiliac insufficiency as described in inclusion criterion number 5

• Participant has bilateral claudication symptoms, but both limbs are equally symptomatic and one side does not show evidence of aortoiliac insufficiency as described in inclusion criterion number 5

• Subject meets the following exclusions based upon modified American College of Sports Medicine criteria for exercise training:

i. Ambulation limited by co-morbid condition other than claudication, for example:1. severe coronary artery disease; 2. angina pectoris; 3. chronic lung disease;4. neurological disorder such as hemiparesis;5. arthritis, or other musculoskeletal conditions including amputation ii. Poorly-controlled hypertension (SBP greater than 180 mm Hg) iii.Poorly-controlled diabetes mellitus iv. Other active significant medical problems such as cancer, known chronic renal disease (serum creatinine greater than 2.0 mg/dl within 60 days or renal replacement therapy), known chronic liver disease or anemia, active substance abuse, or known history of dementia

• Contraindication to exercise testing according to AHA/ACC guideline, specifically:

Acute myocardial infarction (within 3-5 days), unstable angina, uncontrolled cardiac arrhythmias causing symptoms or hemodynamic compromise, active endocarditis, symptomatic severe aortic stenosis, acute pulmonary embolus or pulmonary infarction, acute noncardiac disorder that may affect exercise performance or be aggravated by exercise such as infection, thyrotoxicosis, acute myocarditis or pericarditis, known physical disability that would preclude safe and adequate test performance, known thrombosis of the lower extremity, known left main coronary stenosis or its equivalent, moderate stenotic valvular heart disease, electrolyte abnormalities, known pulmonary hypertension, tachyarrhythmias or bradyarrhythmias, hypertrophic cardiomyopathy, mental impairment leading to inability to cooperate, or high degree atrioventricular block

• Arterial insufficiency of target lesion due to restenosis of an angioplasty/stent or bypass is not eligible

• Recent (less than 3 months) infrainguinal revascularization (surgery or endovascular intervention)

• Recent major surgery in the last 3 months

• Abdominal aortic aneurysm greater than 4 cm or iliac artery aneurysm greater than 1.5 cm is present

• Patients who are pregnant, planning to become pregnant, or lactating

• Unwilling or unable to attend regular (3 times a week) supervised exercise sessions. (Please review this commitment carefully with each prospective participant.)

• Weight greater than 350 lbs or 159 kg (may exceed treadmill and angiography table limits)

• Inability to understand and sign informed consent forms due to cognitive or language barriers (interpreter permitted)

• Absolute contraindication to iodinated contrast due to prior near-fatal anaphylactoid reaction (laryngospasm, bronchospasm, cardiorespiratory collapse, or equivalent) and which would preclude patient from participation in angiographic procedures

• Allergy to stainless steel or nitinol

• Allergy or other intolerance to cilostazol (bleeding history) or history of congestive heart failure [if ejection fraction is shown to be greater than or equal to 50% patient may be enrolled]

• Nonatherosclerotic cause of PAD (fibromuscular dysplasia, dissection, trauma, etc)

• Inability to walk on a treadmill without grade at a speed of at least 2 mph for at least 2 minutes on the first treadmill test

• ST-segment depression greater than 1 mm in any of the standard 12 ECG leads or sustained (greater than 30 seconds) arrhythmia other than tachycardia or occasional premature atrial or ventricular contractions during exercise testing

• Post-exercise systolic blood pressure within the first five minutes after eligibility treadmill test lower than pre-exercise systolic blood pressure

• A peak heart rate greater than 80% of maximum (calculated by subtracting age from 220) while reporting "onset" of claudication symptoms (level 3 or 4) during the second baseline examination

• Repeat treadmill test shows a MWD result that is greater than 25% different than the subject's initial Gardner treadmill test result. Current active involvement in a supervised exercise program (e.g., with a trainer, exercise protocol, and goals, such as in cardiac or pulmonary rehabilitation) for more than 2 weeks within the prior 6 weeks.