Vorapaxar and Lower Extremity Bypass Grafts
Ключевые слова
абстрактный
Описание
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.
Даты
| Последняя проверка: | 12/31/2017 |
| Первый отправленный: | 11/17/2016 |
| Предполагаемая регистрация отправлена: | 11/21/2016 |
| Первое сообщение: | 11/28/2016 |
| Последнее обновление отправлено: | 01/22/2018 |
| Последнее обновление опубликовано: | 01/24/2018 |
| Фактическая дата начала исследования: | 09/30/2017 |
| Предполагаемая дата завершения начальной школы: | 01/09/2018 |
| Предполагаемая дата завершения исследования: | 01/09/2018 |
Состояние или болезнь
Вмешательство / лечение
Drug: Experimental: Vorapaxar
Drug: Placebo Comparator: Placebos
Фаза
Группы рук
| Рука | Вмешательство / лечение |
|---|---|
| Active Comparator: Experimental: Vorapaxar Drug: Vorapaxar 2.08 mg orally daily for a year Other name: Zontivity | Drug: Experimental: Vorapaxar 2.08 mg oral tablet daily |
| Placebo Comparator: Placebo Comparator: Placebos Medication: Matching Placebo Daily tablet | Drug: Placebo Comparator: Placebos Placebo oral tablet daily |
Критерии приемлемости
| Возраст, имеющий право на обучение | 35 Years Чтобы 35 Years |
| Полы, имеющие право на обучение | All |
| Принимает здоровых добровольцев | да |
| Критерии | 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 |
Результат
Основные показатели результатов
1. Bypass Graft Flow Mediated Vasodilation under Fasted Conditions using B-mode ultrasonography on Day 180 for each treatment condition. [6 Months]
Меры вторичного результата
1. 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]
2. Platelet Activation blood testing [30 days]
3. Change in Six Minute Walk Test from Baseline to 1 year [One year]
