Claudication: Exercise Versus Endoluminal Revascularization (CLEVER)

NCT00132743 | Unknown Phase 3 DMC

• 3 other identifiers: 224U01HL081656U01HL077221
• Study Type: interventional
• Target: 119
• Locations: 2 countries
• Sites: 27

Brief Summary

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

Conditions

Cardiovascular Diseases; Peripheral Vascular Diseases; Atherosclerosis

Outcome Measures

Primary Outcomes (3)

• MWD change score

  Aortoiliac revascularization with stent (ST) combined with optimal medical care (OMC) improves maximum walking duration (MWD) compared to optimal medical care alone in patients with claudication and peripheral arterial disease (PAD) who are amenable to peripheral stenting

  Measured at 6 months

• MWD change score

  Regular supervised exercise (SE) combined with optimal medical care (OMC) improves maximum walking duration compared to optimal medical care along in patients with claudication and PAD who are amenable to peripheral stenting.

  Measured at 6 months

• MWD change score

  Aortoiliac revascularization with stent (ST) combined with optimal medical care improves maximum walking duration compared to supervised exercise (SE) combined with optimal medical care in patients with claudication and PAD who are amenable to peripheral stenting.

  Measured at 6 months

Secondary Outcomes (8)

• MWD change score

  Measured at 18 months

• Free-living daily activity

  Measured at 6 and 18 months

• Quality of Life

  Measured at 6 and 18 months

• Cost-effectiveness

  Measured at 18 months

• Cardiovascular risk factors

  Measured at baseline, 6 months, and 18 months

Study Arms (3)

1

ACTIVE COMPARATOR

Optimal Medical Care

Behavioral: Supervised Exercise Therapy; Drug: Cilostazol

2

ACTIVE COMPARATOR

Optimal Medical Care and Supervised Exercise

Device: Stent; Drug: Cilostazol

3

ACTIVE COMPARATOR

Optimal Medical Care and Stent

Device: Stent; Behavioral: Supervised Exercise Therapy

Interventions

Stent DEVICE

Stent

2; 3

Supervised Exercise Therapy BEHAVIORAL

Supervised exercise therapy, three times per week

1; 3

Cilostazol DRUG

Cilostazol, 100 mg twice a day

1; 2

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• Joselyn Cerezo, MD: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (27)

VA Loma Linda

Loma Linda, California, 92357, United States

Location

St. Joseph Hospital

Orange, California, 92868, United States

Location

VA Palo Alto Health Care Systems

Palo Alto, California, 94304, United States

Location

UC Davis

Sacramento, California, 95817, United States

Location

Vasek Polak Research Program

Torrance, California, 90505, United States

Location

Baptist Cardiac and Vascular Institute

Miami, Florida, 33176, United States

Location

Aiyan Diabetes Center

Evans, Georgia, 30809, United States

Location

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

Location

The Iowa Clinic

Des Moines, Iowa, 50309, United States

Location

Rapides Regional Medical Center

Alexandria, Louisiana, 71303, United States

Location

Ochsner Clinic

New Orleans, Louisiana, 70002, United States

Location

Maine Medical Center

Portland, Maine, 04102, United States

Location

Johns Hopkins

Baltimore, Maryland, 21287, United States

Location

VA Ann Arbor

Ann Arbor, Michigan, 48109, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Abbott Northwestern Vascular Center

Minneapolis, Minnesota, 55407, United States

Location

Stony Brook

Stony Brook, New York, 11794-8191, United States

Location

Asheville Cardiology

Asheville, North Carolina, United States

Location

Forsyth-Salem Surgical

Winston-Salem, North Carolina, 27103, United States

Location

Vascular Endovascular Specialists of Ohio

Mansfield, Ohio, 44907, United States

Location

Jobst Vascular

Toledo, Ohio, 43606, United States

Location

Oregon Health Science University (DOTTER)

Portland, Oregon, 97239, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

Providence Medical Research

Spokane, Washington, 99204, United States

Location

Charleston Area Medical Center

Charleston, West Virginia, 25304, United States

Location

Capital Health

Halifax, Nova Scotia, B3H 2Y9, Canada

Location

Related Publications (4)

• Bronas UG, Hirsch AT, Murphy T, Badenhop D, Collins TC, Ehrman JK, Ershow AG, Lewis B, Treat-Jacobson DJ, Walsh ME, Oldenburg N, Regensteiner JG; CLEVER Research Group. Design of the multicenter standardized supervised exercise training intervention for the claudication: exercise vs endoluminal revascularization (CLEVER) study. Vasc Med. 2009 Nov;14(4):313-21. doi: 10.1177/1358863X09102295.

  PMID: 19808716 BACKGROUND

• Murphy TP, Hirsch AT, Cutlip DE, Regensteiner JG, Comerota AJ, Mohler E, Cohen DJ, Massaro J; CLEVER Investigators. Claudication: exercise vs endoluminal revascularization (CLEVER) study update. J Vasc Surg. 2009 Oct;50(4):942-945.e2. doi: 10.1016/j.jvs.2009.04.076. Epub 2009 Aug 5.

  PMID: 19660897 BACKGROUND

• Murphy TP, Cutlip DE, Regensteiner JG, Mohler ER, Cohen DJ, Reynolds MR, Massaro JM, Lewis BA, Cerezo J, Oldenburg NC, Thum CC, Goldberg S, Jaff MR, Steffes MW, Comerota AJ, Ehrman J, Treat-Jacobson D, Walsh ME, Collins T, Badenhop DT, Bronas U, Hirsch AT; CLEVER Study Investigators. Supervised exercise versus primary stenting for claudication resulting from aortoiliac peripheral artery disease: six-month outcomes from the claudication: exercise versus endoluminal revascularization (CLEVER) study. Circulation. 2012 Jan 3;125(1):130-9. doi: 10.1161/CIRCULATIONAHA.111.075770. Epub 2011 Nov 16.

  PMID: 22090168 RESULT

• Reynolds MR, Apruzzese P, Galper BZ, Murphy TP, Hirsch AT, Cutlip DE, Mohler ER 3rd, Regensteiner JG, Cohen DJ. Cost-effectiveness of supervised exercise, stenting, and optimal medical care for claudication: results from the Claudication: Exercise Versus Endoluminal Revascularization (CLEVER) trial. J Am Heart Assoc. 2014 Nov 11;3(6):e001233. doi: 10.1161/JAHA.114.001233.

  PMID: 25389284 DERIVED

MeSH Terms

Conditions

Cardiovascular Diseases; Peripheral Vascular Diseases; Atherosclerosis

Interventions

Stents; Cilostazol

Condition Hierarchy (Ancestors)

Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases

Intervention Hierarchy (Ancestors)

Prostheses and Implants; Equipment and Supplies; Tetrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Don Cutlip, MD

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

• Timothy Murphy, MD

  Rhode Island Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Trials Project Manager

Study Record Dates

• First Submitted: August 19, 2005
• First Posted: August 22, 2005
• Study Start: February 1, 2007
• Primary Completion: July 1, 2013
• Study Completion: July 1, 2013
• Last Updated: April 25, 2013

Record last verified: 2013-04

Locations

CA (1); US (26)