Claudication: Exercise Versus Endoluminal Revascularization (CLEVER)
The purpose of this study is to compare the effectiveness of aortic stent surgery versus exercise therapy in individuals with aortoiliac insufficiency.
Peripheral Vascular Diseases
Behavioral: Supervised Exercise Therapy
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Claudication: Exercise Versus Endoluminal Revascularization (CLEVER)|
- MWD change score [ Time Frame: Measured at 6 months ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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.
- MWD change score [ Time Frame: Measured at 18 months ] [ Designated as safety issue: No ]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.
- Free-living daily activity [ Time Frame: Measured at 6 and 18 months ] [ Designated as safety issue: No ]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)
- Quality of Life [ Time Frame: Measured at 6 and 18 months ] [ Designated as safety issue: No ]To examine treatment effects on patient-perceived health-related quality of life (physical function) between all groups at 6 and 18 months
- Cost-effectiveness [ Time Frame: Measured at 18 months ] [ Designated as safety issue: No ]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.
- Cardiovascular risk factors [ Time Frame: Measured at baseline, 6 months, and 18 months ] [ Designated as safety issue: No ]To evaluate the impact of cardiovascular disease risk factors by comparing these values at baseline, 6 months, and 18 months.
- Interaction effect [ Time Frame: Measured at 18 months ] [ Designated as safety issue: No ]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.
- Major adverse peripheral events [ Time Frame: Measured from randomization to 18 months ] [ Designated as safety issue: Yes ]To track major adverse peripheral events (MAPEs) associated with aortoiliac stenting and femoropopliteal endovascular intervention.
- Major complication [ Time Frame: Measured from randomization to 18 months ] [ Designated as safety issue: Yes ]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).
|Study Start Date:||February 2007|
|Estimated Study Completion Date:||July 2013|
|Estimated Primary Completion Date:||July 2013 (Final data collection date for primary outcome measure)|
Active Comparator: 1
Optimal Medical Care
Behavioral: Supervised Exercise Therapy
Supervised exercise therapy, three times per weekDrug: Cilostazol
Cilostazol, 100 mg twice a day
Active Comparator: 2
Optimal Medical Care and Supervised Exercise
Cilostazol, 100 mg twice a day
Active Comparator: 3
Optimal Medical Care and Stent
StentBehavioral: Supervised Exercise Therapy
Supervised exercise therapy, three times per week
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.
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.
Show 27 Study Locations
|Principal Investigator:||Don Cutlip, MD||Brigham and Women's Hospital|
|Principal Investigator:||Timothy Murphy, MD||Rhode Island Hospital|