Cardiovascular DiseasesPhase 3CLEVERNCT00132743
Claudication: Exercise Versus Endoluminal Revascularization (CLEVER)
A Phase 3 study testing Stent, Supervised Exercise Therapy and Cilostazol in people with Cardiovascular Diseases and Peripheral Vascular Diseases, run by Joselyn Cerezo, MD at 27 sites in 2 countries.
Trial summary
The purpose of this study is to compare the effectiveness of aortic stent surgery versus exercise therapy in individuals with aortoiliac insufficiency. Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Cardiovascular Diseases, Peripheral Vascular Diseases, Atherosclerosis
- What is being tested?
- Stent, Supervised Exercise Therapy and Cilostazol
- Type of treatment
- Medical device, Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 119 participants
- Where
- 27 sitesin 2 countries
- Study dates
- Feb 2007to Jul 2013
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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:
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- 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.
Trial locations and contacts
27 sites in 2 countries.
27 sites in 2 countries
United States26 sites
Rapides Regional Medical Center
Alexandria, Louisiana, 71303
VA Ann Arbor
Ann Arbor, Michigan, 48109
Asheville Cardiology
Asheville, North Carolina
Johns Hopkins
Baltimore, Maryland, 21287
Charleston Area Medical Center
Charleston, West Virginia, 25304
Northwestern Memorial Hospital
Chicago, Illinois, 60611
The Iowa Clinic
Des Moines, Iowa, 50309
Henry Ford Hospital
Detroit, Michigan, 48202
Aiyan Diabetes Center
Evans, Georgia, 30809
VA Loma Linda
Loma Linda, California, 92357
Vascular Endovascular Specialists of Ohio
Mansfield, Ohio, 44907
Baptist Cardiac and Vascular Institute
Miami, Florida, 33176
Abbott Northwestern Vascular Center
Minneapolis, Minnesota, 55407
Ochsner Clinic
New Orleans, Louisiana, 70002
St. Joseph Hospital
Orange, California, 92868
VA Palo Alto Health Care Systems
Palo Alto, California, 94304
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Maine Medical Center
Portland, Maine, 04102
Oregon Health Science University (DOTTER)
Portland, Oregon, 97239
Rhode Island Hospital
Providence, Rhode Island, 02903
UC Davis
Sacramento, California, 95817
Providence Medical Research
Spokane, Washington, 99204
Stony Brook
Stony Brook, New York, 11794-8191
Jobst Vascular
Toledo, Ohio, 43606
Vasek Polak Research Program
Torrance, California, 90505
Forsyth-Salem Surgical
Winston-Salem, North Carolina, 27103
About this study
The purpose of this study is to compare the effectiveness of aortic stent surgery versus exercise therapy in individuals with aortoiliac insufficiency.
Read the detailed description
BACKGROUND:
Peripheral arterial disease (PAD) is a major source of morbidity and mortality, particularly in older individuals. Despite its high prevalence, clinicians often fail to diagnose PAD, particularly in patients who do not have classic claudication symptoms. Even in those individuals with documented PAD, cardiac risk factors are not often aggressively treated, and only a minority of patients receive pharmacologic therapy with cilostazol. Although there is a growing body of literature demonstrating the value of exercise rehabilitation in individuals with peripheral vascular disease and claudication, exercise rehabilitation is not often prescribed as supervised exercise rehabilitation for claudication, is not reimbursed by Medicare, and is rarely covered by private insurance. Therefore, few individuals with PAD and intermittent claudication have access to supervised exercise rehabilitation.
The use of surgical intervention and stent placement to improve blood flow in patients who do not have ischemic pain at rest or limb-threatening ischemia (Fontaine class III or IV) remains controversial. There is data suggesting that patients with intermittent claudication who have had revascularization with stents have improved exercise capacity and walking times. However, the patients in the various studies often differ substantially in their clinical characteristics, and a variety of techniques were employed, including balloon angioplasty and stents, which makes it difficult to come to a definitive conclusion about the relative efficacy of stenting to improve functional performance. Additionally, to our knowledge, the combination of stent revascularization with supervised exercise rehabilitation has not been studied.
DESIGN NARRATIVE:
The broad objective of the study is to optimize physical functioning, increase activity levels, and reduce cardiovascular disease risk in older individuals with PAD. The specific aim of the trial is to test the primary hypothesis that aortoiliac stenting/pharmacotherapy improves maximum walking duration (MWD) better than supervised exercise rehabilitation/exercise maintenance/pharmacotherapy for those with aortoiliac artery obstruction at 6 months. Other aims are to compare these two treatment groups with two other treatment groups, optimal medical care/pharmacotherapy and combined stent plus supervised exercise rehabilitation, at 6 months, and to compare all 4 groups with regard to the following variables: MWD change score at 18 months, changes in free-living daily activity levels, patient-perceived quality of life (QoL), and cost-effectiveness. The study also will perform exploratory analyses of demographic and biochemical risk factors for atherosclerosis, including body mass index (BMI), blood pressure, lipid profile, hemoglobin Alc (HgbAlc), fibrinogen, and C-reactive protein. An estimated 252 patients (at up to 30 study sites) with aortoiliac insufficiency and intermittent claudication will be randomly divided into four groups: optimal medical care/pharmacotherapy, supervised exercise rehabilitation/maintenance/pharmacotherapy, stent/pharmacotherapy, and stent/supervised exercise rehabilitation/pharmacotherapy. Recruitment will be performed over 28 months and patients will be followed for 18 months; the total study duration will be 5 years.
- Being tested
- Stent, Supervised Exercise Therapy, Cilostazol
- Medical subject headings
- Cardiovascular Diseases, Peripheral Vascular Diseases, Atherosclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
StentDevice
Stent
Supervised Exercise TherapyBehavioural
Supervised exercise therapy, three times per week
CilostazolDrug
Cilostazol, 100 mg twice a day
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | Optimal Medical Care Receives: Behavioral: Supervised Exercise Therapy; Drug: Cilostazol |
| 2 | Active comparator | Optimal Medical Care and Supervised Exercise Receives: Device: Stent; Drug: Cilostazol |
| 3 | Active comparator | Optimal Medical Care and Stent Receives: Device: Stent; Behavioral: Supervised Exercise Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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: 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: 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: Measured at 6 months
Secondary outcomes (8)
MWD change score
To evaluate the mid-term durability of any treatment effect by performing pair-wise comparison of change in MWD between baseline and 18 month time points among all three treatment groups of primary interest.
Measured: Measured at 18 months
Free-living daily activity
To assess a treatment effect on free-living daily activity levels of any treatment group, comparing baseline electronic step monitors values with those obtained at both follow up intervals (6 and 18 months)
Measured: Measured at 6 and 18 months
Quality of Life
To examine treatment effects on patient-perceived health-related quality of life (physical function) between all groups at 6 and 18 months
Measured: Measured at 6 and 18 months
Cost-effectiveness
To Examine inpatient and outpatient costs associated with the three treatment strategies, and to evaluate the relative cost-benefit by calculating incremental cost-effectiveness and cost effectiveness acceptability curves using health utility change in the denominator.
Measured: Measured at 18 months
Cardiovascular risk factors
To evaluate the impact of cardiovascular disease risk factors by comparing these values at baseline, 6 months, and 18 months.
Measured: Measured at baseline, 6 months, and 18 months
Interaction effect
To evaluate the interaction effect, if any, of gender or race on improvements in MWD, improvement in free-living daily activities, and quality-of-life.
Measured: Measured at 18 months
Major adverse peripheral events
To track major adverse peripheral events (MAPEs) associated with aortoiliac stenting and femoropopliteal endovascular intervention.
Measured: Measured from randomization to 18 months
Major complication
Rate of major complication defined as any occurrence of death, myocardial infarction, amputation of the target limb (limb treated in this study), or occurrence of critical limb ischemia or repeat target limb revascularization (TLiR).
Measured: Measured from randomization to 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Aug 2005 (estimated)
- Study startFeb 2007
- Primary completionJul 2013 (estimated)
- Study completionJul 2013 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Cardiovascular DiseasesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 119 participants (actual)
Sponsor and investigators
- Lead sponsor
- Joselyn Cerezo, MD
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Sponsor-investigator, Joselyn Cerezo, MD, Rhode Island Hospital
- Investigators
- Don Cutlip, MD, Principal investigator, Brigham and Women's HospitalTimothy Murphy, MD, Principal investigator, Rhode Island Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00132743
- Sponsor's protocol ID
- 224
- Other IDs
- U01HL081656, U01HL077221
- Acronym
- CLEVER
- Status last verified
- Apr 2013
- First submitted
- 19 Aug 2005
- Last updated
- 25 Apr 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 19808716Murphy 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.
PubMed 19660897Murphy 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.
PubMed 22090168Reynolds 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.
PubMed 25389284
Study at a glance
From the registry record, last updated by the sponsor on 25 Apr 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Claudication: Exercise Versus Endoluminal Revascularization (CLEVER)
- ClinicalTrials.gov ID
- NCT00132743
- Acronym / sponsor ID
- CLEVER / 224
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 119 participants (actual)
- Lead sponsor
- Joselyn Cerezo, MDUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Feb 2007
- Primary completion
- Jul 2013 (estimated)
- Study completion
- Jul 2013 (estimated)
- First posted
- 22 Aug 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to compare the effectiveness of aortic stent surgery versus exercise therapy in individuals with aortoiliac insufficiency.
Detailed description
BACKGROUND:
Peripheral arterial disease (PAD) is a major source of morbidity and mortality, particularly in older individuals. Despite its high prevalence, clinicians often fail to diagnose PAD, particularly in patients who do not have classic claudication symptoms. Even in those individuals with documented PAD, cardiac risk factors are not often aggressively treated, and only a minority of patients receive pharmacologic therapy with cilostazol. Although there is a growing body of literature demonstrating the value of exercise rehabilitation in individuals with peripheral vascular disease and claudication, exercise rehabilitation is not often prescribed as supervised exercise rehabilitation for claudication, is not reimbursed by Medicare, and is rarely covered by private insurance. Therefore, few individuals with PAD and intermittent claudication have access to supervised exercise rehabilitation.
The use of surgical intervention and stent placement to improve blood flow in patients who do not have ischemic pain at rest or limb-threatening ischemia (Fontaine class III or IV) remains controversial. There is data suggesting that patients with intermittent claudication who have had revascularization with stents have improved exercise capacity and walking times. However, the patients in the various studies often differ substantially in their clinical characteristics, and a variety of techniques were employed, including balloon angioplasty and stents, which makes it difficult to come to a definitive conclusion about the relative efficacy of stenting to improve functional performance. Additionally, to our knowledge, the combination of stent revascularization with supervised exercise rehabilitation has not been studied.
DESIGN NARRATIVE:
The broad objective of the study is to optimize physical functioning, increase activity levels, and reduce cardiovascular disease risk in older individuals with PAD. The specific aim of the trial is to test the primary hypothesis that aortoiliac stenting/pharmacotherapy improves maximum walking duration (MWD) better than supervised exercise rehabilitation/exercise maintenance/pharmacotherapy for those with aortoiliac artery obstruction at 6 months. Other aims are to compare these two treatment groups with two other treatment groups, optimal medical care/pharmacotherapy and combined stent plus supervised exercise rehabilitation, at 6 months, and to compare all 4 groups with regard to the following variables: MWD change score at 18 months, changes in free-living daily activity levels, patient-perceived quality of life (QoL), and cost-effectiveness. The study also will perform exploratory analyses of demographic and biochemical risk factors for atherosclerosis, including body mass index (BMI), blood pressure, lipid profile, hemoglobin Alc (HgbAlc), fibrinogen, and C-reactive protein. An estimated 252 patients (at up to 30 study sites) with aortoiliac insufficiency and intermittent claudication will be randomly divided into four groups: optimal medical care/pharmacotherapy, supervised exercise rehabilitation/maintenance/pharmacotherapy, stent/pharmacotherapy, and stent/supervised exercise rehabilitation/pharmacotherapy. Recruitment will be performed over 28 months and patients will be followed for 18 months; the total study duration will be 5 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Behavioral: Supervised Exercise Therapy, Drug: CilostazolOptimal Medical Care |
| 2 | Active comparator | Device: Stent, Drug: CilostazolOptimal Medical Care and Supervised Exercise |
| 3 | Active comparator | Device: Stent, Behavioral: Supervised Exercise TherapyOptimal Medical Care and Stent |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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):
- 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.
Key exclusion criteria (25 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| StentStent | Device | 2, 3 |
| Supervised Exercise TherapySupervised exercise therapy, three times per week | Behavioural | 1, 3 |
| CilostazolCilostazol, 100 mg twice a day | Drug | 1, 2 |
Primary outcome
MWD change score
Time frame: Measured at 6 months
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
MWD change score
Time frame: Measured at 6 months
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.
MWD change score
Time frame: Measured at 6 months
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.
8 secondary outcomes
MWD change score
Time frame: Measured at 18 months
Free-living daily activity
Time frame: Measured at 6 and 18 months
Quality of Life
Time frame: Measured at 6 and 18 months
Cost-effectiveness
Time frame: Measured at 18 months
Cardiovascular risk factors
Time frame: Measured at baseline, 6 months, and 18 months
Interaction effect
Time frame: Measured at 18 months
Major adverse peripheral events
Time frame: Measured from randomization to 18 months
Major complication
Time frame: Measured from randomization to 18 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Apr 2013.
- Background: PubMed 19808716Bronas 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.
- Background: PubMed 19660897Murphy 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.
- Results publication: PubMed 22090168Murphy 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.
- Derived from this study: PubMed 25389284Reynolds 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Don Cutlip, MD principal investigator
Brigham and Women's Hospital
Timothy Murphy, MD principal investigator
Rhode Island Hospital
27 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Stent, Supervised Exercise Therapy and Cilostazol in people with Cardiovascular Diseases and Peripheral Vascular Diseases, run by Joselyn Cerezo, MD at 27 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 25 Apr 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 27 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
MWD change score (time frame: Measured at 6 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00132743, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Apr 2013.