Peripheral Arterial Disease
Conditions
Keywords
intermittent claudication, randomized controlled trial
Brief summary
This is a Phase 4, randomized clinical trial to evaluate whether addition of Vorapaxar 2.08 mg daily vs. placebo daily on background antiplatelet therapy, prescribed for 6 months to patients with established peripheral artery disease (PAD) and Intermittent Claudication (IC) treated with standard medical therapy (SMT) would lead to an improvement in the peak walking time (PWT).
Detailed description
Primary trial objective: To evaluate whether addition of Vorapaxar 2.08 mg daily vs. placebo daily on background antiplatelet therapy, prescribed for 6 months to patients with established PAD and IC treated with standard medical therapy (SMT) would lead to an improvement in the peak walking time (PWT) Study endpoints Primary endpoint: Change from baseline to 6 months in the PWT on a graded treadmill test (GTT per Gardner protocol) between participants enrolled in the test and control arms of the study Secondary endpoints * Change from baseline to 6 months in the claudication onset time (COT) on GTT between participants enrolled in the test and control arms of the study. * Change from baseline to 6 months in the walking impairment questionnaire distance scores (WIQ) between participants enrolled in the test and control arms of the study. * Change from baseline to 6 months in self-reported quality of life score using the Medical Outcomes Study 12-Item Short form survey (SF-12) between participants enrolled in the test and control arms of the study Tertiary endpoints * The first occurrence of clinically indicated lower extremity endovascular or surgical revascularization procedure during the entire study duration post-randomization in participants enrolled in the test or control arms of the study. * The first occurrence of all-cause death, MI, ischemic stroke during the entire study duration post-randomization in participants enrolled in the test or control arms of the study. * The first occurrence of severe bleeding defined according to the Global Utilization of Streptokinase and Tissue plasminogen activator for Occluded coronary arteries (GUSTO) classification during the entire study duration post-randomization in participants enrolled in the test or control arms of the study.
Interventions
DRUGPlacebo + background APT + SMT
Placebo drug therapy combined with standard medical therapy combined with Antiplatelet therapy (Aspirin therapy)
DRUGVorapaxar 2.08 mg/d + background APT + SMT.
Vorapaxar 2.08 mg/d combined with standard medical therapy combined with Antiplatelet therapy (Aspirin therapy)
Sponsors
North Texas Veterans Healthcare System
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
Pre-screening criteria * Laboratory values available ≤ 1 year of the date of screening: hemoglobin ≥9g, platelet count \>50,000 mm3 or \<600,000 mm3 * No history of stroke or transient ischemic attack (TIA) * No allergy to aspirin * ≥40 years of age * Presence of documented PAD by ABI \<0.80 at rest or ≥20% drop in claudication limited exercise ABI in any limb and one of the following criteria in the corresponding limb: i.Prior surgical and/or endovascular lower extremity intervention (infra-renal aorta to pedal arteries) ii. Known presence of flow-limiting stenosis (≥70%) by clinically indicated angiography, computed tomographic (CT) or magnetic resonance imaging (MRI) tests or by Duplex ultrasonography (DUS) defined standard clinical criteria in lower extremity arteries * Documented IC Rutherford/Becker (RC) category ≥2 * Presence of any one of the listed classes of agents \[angiotensin converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB), lipid lowering therapy, aspirin and beta-blocker drugs\]-No MI or percutaneous coronary intervention (PCI) with DES within the past 11 months * No planned surgical or endovascular procedures other than for the treatment of IC for the expected duration of the study * No warfarin or other chronic oral anticoagulant use within the last 14 days * No use of ticagrelor, clopidogrel, prasugrel or ticlopidine within last 7 days * No contraindication(s) to the use of antithrombin or antiplatelet agents (history of intra-cerebral hemorrhage or ICH, presence of intracerebral mass, recent or \<12 weeks gastrointestinal bleed requiring blood transfusion, any blood transfusion within the last 6 weeks, any trauma requiring surgery within the last 4 weeks or any surgical or endovascular procedure within the last 4 weeks * No use of cilostazol and/or pentoxyphilline within last 7 days * Severe psychiatric or behavioral illness that in the judgement of the investigator precludes study participation * No history of major or minor amputation * Severe heart, vascular and lung disease in the discretion of the investigator that precludes study participation. * Ability to walk for at least 15 min/day, at least 3 days/week, at ≥20 steps/min Inclusion criteria * Treadmill PWT= 2-10 min on Gardner protocol * Estimated survival ≥1 year in the judgment of the site investigator * Use of at least one aspirin dose within at least 5 days prior to randomization at 325 mg dose in aspirin naïve patients (0-5 days of prior aspirin use) or at least one aspirin dose prior to randomization at 81 mg dose in patients on chronic (\>5 days) aspirin therapy (at clinically indicated doses). * Presence of any one of the listed classes of agents \[angiotensin converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB), lipid lowering therapy, aspirin and beta-blocker drugs\]
Exclusion criteria
* MI or percutaneous coronary intervention (PCI) with DES within the past 11 months * Positive pregnancy test * Planned surgical or endovascular procedures other than for the treatment of IC * Warfarin or other chronic oral anticoagulant use within 14 days * Use of Ticagrelor, Clopidogrel, Prasugrel or Ticlopidine within 7 days * Contraindication(s) to the use of antithrombin or antiplatelet agents (history of intra-cerebral hemorrhage or ICH, presence of intracerebral mass, recent or \<12 weeks gastrointestinal bleed requiring blood transfusion, any blood transfusion within the last 6 weeks, any trauma requiring surgery within the last 4 weeks or any surgical or endovascular procedure within the last 4 weeks * Use of cilostazol and/or pentoxyphilline within 7 days
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change from baseline to 6 months in the PWT on a graded treadmill test (GTT per Gardner protocol) between participants enrolled in the test and control arms of the study | 6 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline to 6 months in the claudication onset time (COT) on GTT between participants enrolled in the test and control arms of the study. | 6 months | Change from baseline to 6 months in the walking impairment questionnaire distance scores (WIQ) between participants enrolled in the test and control arms of the study. Change from baseline to 6 months in self-reported quality of life score using the Medical Outcomes Study 12-Item Short form survey (SF-12) between participants enrolled in the test and control arms of the study. |
Countries
United States
Contacts
Primary ContactIshita Tejani, BDS, MS, MSPH
Outcome results
None listed