A Phase 4 interventional study of Vorapaxar and Placebos in Peripheral Artery Disease, sponsored by Vanderbilt University. Withdrawn. Open to participants aged 35 Years to 75 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2018-01-25.
Sponsored by Vanderbilt University · Phase 4, Interventional, and Other
There are no medical therapies indicated for reduction of limb ischemic events. Studies of dual-antiplatelet therapy with aspirin and clopidogrel versus aspirin alone (CASPAR) as well as studies of systemic anticoagulation (WAVE) have shown no benefit for either strategy in the reduction in limb vascular events. Surgical bypass grafting involves harvesting of the vein, warm ischemia with disruption of vaso vasorum, ischemia-reperfusion, and finally heightened hemodynamic stress in the new arterial environment. Vein grafts rapidly remodel in response to the increase in blood flow and pressure in an attempt to normalize them into physiological range. The investigators have previously identified 3 distinct temporal phases of the remodeling process: During the first 30 days following implantation is a critical period of luminal enlargement which appears to be an endothelium-independent process. The second phase occurs between 1 and 3 months and represents a period of stiffening of the vein graft indicating synthesis of fibrous proteins. The third period is referred to as biochemical remodeling wherein the vein recovers clinically measureable endothelial function. It is likely diabetes mellitus impacts each of these phases. TRA2°P-TIMI 50 demonstrated a reduction in acute limb ischemic (ALI) events (42% reduction) and urgent peripheral arterial revascularizations (35% reduction), a finding unique among medical therapies. While the temporal trend in reduction in ALI events occurred early and late after exposure suggestion an antithrombotic mechanism, the reduction in elective revascularization occurred later suggested beneficial effects beyond platelet inhibition. The purpose of this trial is to study the physiological impact of vorapaxar on lower extremity bypass graft maturation and function.
Peripheral artery disease (PAD) is characterized by atherosclerotic occlusive disease of the lower extremities. More than 8 million Americans and 200 million people globally have PAD. Recent data reveal a prevalence of 15% in the MEDICARE population. In populations at risk, patients with a history of diabetes or cigarette smoking, the risk may rise as high as 30%. In addition to the heightened risk of myocardial infarction and stroke, PAD increases the risk of lower extremity claudication and critical limb ischemia. Lower extremity bypass grafting is an important method of restoring blood flow to the distal limb, reducing symptoms of claudication, and preventing amputation in patients with severe PAD.
Vorapaxar is a protease activated receptor (PAR)-1 antagonist that inhibits thrombin activation of the PAR-1 receptor. Vorapaxar has been FDA approved for patients with PAD to reduce the rate of cardiovascular death, MI, stroke, and urgent coronary revascularization. It is prohibited in patients with a previous stroke. In addition, patients treated with vorapaxar were noted to have a significant reduction in the rates of acute limb ischemia. This study will be a randomized, double blind, placebo-controlled randomized study of vorapaxar vs. placebo in 80 patients undergoing femoral-popliteal bypass grafting for Rutherford 3 - 5 disease.
Baseline visit: Informed consent will be signed. Vital signs will be taken and blood drawn fasting for baseline values.
First visit, pre-surgery: Blood will be drawn for platelet activation testing. A 6 minute walk test will be performed. Brachial artery reactivity testing will be performed. An ankle-brachial index will be performed.
30 days: Platelet testing will be performed. 90 days: Limited history and physical exam. 180 days: Limited history and exam, blood draw for biomarkers, brachial artery reactivity testing. Vein bypass graft reactivity testing.
360 days: 6 minute walk test and ankle brachial index will be performed.
Randomization: The Investigational Pharmacy will create a block randomization. Patients in the active treatment group will receive vorapaxar 2.08 mg daily or matching placebo. Treatment will continue for 1 year.
In addition, 20 healthy subjects to serve as a control population to define normal parameters during a single visit day. The healthy subjects will not be administered vorapaxar or placebo.
1,542 studies on the registry are indexed under Peripheral Arterial Disease; 282 are open to participants now.
Browse Peripheral Arterial Disease studies →Vanderbilt University is the lead sponsor of 508 studies on the registry; 19 are open to participants now.
Of its 7 completed or terminated interventional studies of FDA-regulated products, 5 (71%) have results posted.
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Exclusion Criteria:
Drug: Vorapaxar 2.08 mg orally daily for a year Other name: Zontivity
Drug: Vorapaxar
Medication: Matching Placebo Daily tablet
Drug: Placebos
2.08 mg oral tablet daily
Also known as: Zontivity
Placebo oral tablet daily
Also known as: Placebo
Bypass Graft Flow Mediated Vasodilation under Fasted Conditions using B-mode ultrasonography on Day 180 for each treatment condition.
Ultrasonographic evaluation of the graft before and after sphygmomanometric cuff inflation on the calf is performed and the measure of interest is percent increase in vein graft diameter.
Time frame: 6 Months
Change From Baseline in Flow Mediated Vasodilation (FMD) Under Fasted Condition on Day 180 [ Time Frame: baseline and day 180 for each treatment arm ]
Ultrasonographic evaluation of the graft before and after sphygmomanometric cuff inflation on the arm is performed and the measure of interest is percent increase in brachial artery diameter.
Time frame: 6 Months
Platelet Activation blood testing
The investigators will be measuring levels of platelet dilysyl-MDA cross-links 30 days after treatment initiation. Higher levels indicate more platelet activation.
Time frame: 30 days
Change in Six Minute Walk Test from Baseline to 1 year
The distance walked in a 100 foot hallway in 6 minutes.
Time frame: One year
No study locations are listed for this record.
Plan to share: No — There is no plan to share IPD at this time.
No publications or documents are linked to this record.
This study is withdrawn, as verified in Jan 2018. You cannot join it, but the record below documents what was studied.
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