Vorapaxar and Lower Extremity Bypass Grafts

• Status: Withdrawn
• Trial end date: 2018-01-10
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Vanderbilt University; Vanderbilt University Medical Center
• Collaborator: Merck Sharp & Dohme Corp.
• Treatments: Vorapaxar

Criteria

Inclusion Criteria:

• Male or female, age 35 years or older

• Atherosclerotic, infrainguinal PAD

• Rutherford classes 3-5 planned for lower extremity bypass grafting

• Adequate inflow into the index femoral artery

• Adequate popliteal, tibial, or pedal revascularization target

• Willing to comply with protocol, attend follow-up appointments, complete all study assessments, and provide informed consent

Exclusion Criteria:

• Complete occlusion of the iliac artery

• Aortoiliac occlusive disease or severe common femoral artery disease

• Presence of a femoral, popliteal or tibial aneurysm of the index limb

• Life expectancy less than 2 years

• A vascular disease prognosis that includes an anticipated above ankle amputation on index limb within 4 weeks of index procedure

• Renal dysfunction defined as MDRD eGFR ≤ 30ml/min/173 m2 at the time of screening

• Currently on dialysis or history of a renal transplant

• A documented hypercoagulable state

• Nonatherosclerotic occlusive disease

• Any prior infrainguinal revascularization

• Current immunosuppressive medication, chemotherapy or radiation therapy

• Absolute contraindication to iodinated contrast

• Women who are pregnant

• Women who are nursing