Vorapaxar and Lower Extremity Bypass Grafts
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|ClinicalTrials.gov Identifier: NCT02975583|
Recruitment Status : Withdrawn (We could not secure adequate medication)
First Posted : November 29, 2016
Last Update Posted : January 25, 2018
|Condition or disease||Intervention/treatment||Phase|
|Peripheral Artery Disease||Drug: Vorapaxar Drug: Placebos||Phase 4|
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 :||Interventional (Clinical Trial)|
|Actual Enrollment :||0 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||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|
|Actual Study Start Date :||October 1, 2017|
|Actual Primary Completion Date :||January 10, 2018|
|Actual Study Completion Date :||January 10, 2018|
Active Comparator: Experimental: Vorapaxar
Drug: Vorapaxar 2.08 mg orally daily for a year Other name: Zontivity
2.08 mg oral tablet daily
Other Name: Zontivity
Placebo Comparator: Placebo Comparator: Placebos
Medication: Matching Placebo Daily tablet
Placebo oral tablet daily
Other Name: Placebo
- 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.
- 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.
- 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.
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02975583
|Principal Investigator:||Joshua A Beckman||Vanderbilt University Medical Center|