Excellence In Peripheral Artery Disease Thrombin Receptor Antagonist Intervention In Claudication Evaluation (XLPAD-TRACE Trial)

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