- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02975583
Vorapaxar and Lower Extremity Bypass Grafts
A Double-blind, Randomized, Parallel Design Two Center Study to Compare the Effect of Vorapaxar vs. Placebo on Lower Extremity Vein Graft Maturation, Remodeling, and Function
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
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.
Study Type
Phase
- Phase 4
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Other
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Experimental: Vorapaxar
Drug: Vorapaxar 2.08 mg orally daily for a year Other name: Zontivity
|
2.08 mg oral tablet daily
Other Names:
|
Placebo Comparator: Placebo Comparator: Placebos
Medication: Matching Placebo Daily tablet
|
Placebo oral tablet daily
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Bypass Graft Flow Mediated Vasodilation under Fasted Conditions using B-mode ultrasonography on Day 180 for each treatment condition.
Time Frame: 6 Months
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change From Baseline in Flow Mediated Vasodilation (FMD) Under Fasted Condition on Day 180 [ Time Frame: baseline and day 180 for each treatment arm ]
Time Frame: 6 Months
|
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.
|
6 Months
|
Platelet Activation blood testing
Time Frame: 30 days
|
The investigators will be measuring levels of platelet dilysyl-MDA cross-links 30 days after treatment initiation.
Higher levels indicate more platelet activation.
|
30 days
|
Change in Six Minute Walk Test from Baseline to 1 year
Time Frame: One year
|
The distance walked in a 100 foot hallway in 6 minutes.
|
One year
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Joshua A Beckman, Vanderbilt University Medical Center
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 161925
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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