Vorapaxar and Lower Extremity Bypass Grafts

NCT02975583 | Withdrawn Phase 4

• 1 other identifier: 161925
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Peripheral Artery Disease

Keywords

Atherosclerosis

Outcome Measures

Primary Outcomes (1)

• 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.

  6 Months

Secondary Outcomes (3)

• Change From Baseline in Flow Mediated Vasodilation (FMD) Under Fasted Condition on Day 180 [ Time Frame: baseline and day 180 for each treatment arm ]

  6 Months

• Platelet Activation blood testing

  30 days

• Change in Six Minute Walk Test from Baseline to 1 year

  One year

Study Arms (2)

Experimental: Vorapaxar

ACTIVE COMPARATOR

Drug: Vorapaxar 2.08 mg orally daily for a year Other name: Zontivity

Drug: Vorapaxar

Placebo Comparator: Placebos

PLACEBO COMPARATOR

Medication: Matching Placebo Daily tablet

Drug: Placebos

Interventions

Vorapaxar DRUG

2.08 mg oral tablet daily

Also known as: Zontivity

Experimental: Vorapaxar

Placebos DRUG

Placebo oral tablet daily

Also known as: Placebo

Placebo Comparator: Placebos

Eligibility Criteria

• Age: 35 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Vanderbilt University: lead
• Merck Sharp & Dohme LLC: collaborator

MeSH Terms

Conditions

Peripheral Arterial Disease; Atherosclerosis

Interventions

vorapaxar

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases

Study Officials

• Joshua A Beckman

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: November 18, 2016
• First Posted: November 29, 2016
• Study Start: October 1, 2017
• Primary Completion: January 10, 2018
• Study Completion: January 10, 2018
• Last Updated: January 25, 2018

Record last verified: 2018-01

Data Sharing

• IPD Sharing: Will not share