Efficacy and safety of rivaroxaban in reducing the risk of major thrombotic vascular events in subjects with peripheral artery disease undergoing peripheral revascularization procedures of the lower extremities

INTERVENTION: Trade Name: Xarelto 2.5 mg film‐coated tablets Product Name: Rivaroxaban 2.5mg Product Code: BAY 59‐7939 Pharmaceutical Form: Film‐coated tablet INN or Proposed INN: RIVAROXABAN CAS Number: 366789‐02‐8 Current Sponsor code: BAY 59‐7939 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 2.5‐ Pharmaceutical form of the placebo: Film‐coated tablet Route of administration of the placebo: Oral use CONDITION: Peripheral artery disease ; MedDRA version: 19.1 Level: LLT Classification code 10053375 Term: Peripheral revascularization System Organ Class: 100000004865 Therapeutic area: Diseases [C] ‐ Cardiovascular Diseases [C14] PRIMARY OUTCOME: Main Objective: To evaluate whether rivaroxaban added to acetylsalicylic acid (ASA) is superior to ASA alone in reducing the risk of major thrombotic vascular events (defined as myocardial infarction (MI), ischemic stroke, cardiovascular (CV) death, acute limb ischemia (ALI), and major amputation of a vascular etiology) in symptomatic PAD patients undergoing lower extremity revascularization procedure.; ; To evaluate the overall safety and tolerability of rivaroxaban added to ASA compared to ASA alone. Primary end point(s): 1. Time from randomization to the first occurrence of any of the following major thrombotic vascular events: MI (Myocardial infarction), ischemic stroke, CV (Cardiovascular) death, ALI (Acute limb ischemia), and major amputation; ; 2. Time from randomization to first occurrence of major bleeding events according to the Thrombolysis in Myocardial Infarction (TIMI) classification Secondary Objective: ‐ To evaluate whether rivaroxaban + ASA is superior to ASA alone in reducing the risk of MI, ischemic stroke, coronary heart disease mortality, ALI, and major amputation of a vascular etiology;; ‐ To evaluate whether rivaroxaban + ASA is superior to ASA alone in reducing the risk of an unplanned index limb revascularization for recurrent limb ischemia (subsequent index leg revascularizations that were not planned or considered as part of the initial treatment plan at the time of randomization); ‐ To evaluate whether rivaroxaban + ASA is superior to ASA alone in reducing the risk of MI, ischemic stroke, all‐cause mortality, ALI, and major amputation of a vascular etiology; ; ‐ To evaluate whether rivaroxaban + ASA is superior to ASA alone in reducing the risk of vascular hospitalizations for a coronary or peripheral event (either limb) of a thrombotic nature;; ; See Protocol section 4 for the full list of objectives Timepoint(s) of evaluation of this end point: Approximately 2 years SECONDARY OUTCOME: Secondary end point(s): 1. Time from randomization to first occurrence of an index limb revascularization ; ; 2. Time from randomization to the first occurrence of an index limb revascularization (subsequent index leg revascularization that was not planned or considered as part of the initial treatment plan at the time of randomization) ; ; 3. Time from randomization to first occurrence of myocardial infarction, ischemic stroke, all‐cause mortality,acute limb ; ischemia, and major amputation of a vascular etiology ; ; 4. Time from randomization to first occurrence of hospitalization for a coronary or peripheral cause (either lower limb) of a thrombotic nature ; ; 5. Time from randomization to first occurrence of myocardial infarction, all‐cause stroke, cardiovascular death, acute limb ischemia, and major amputation of a vascular etiology ; ; 6. Time from randomization to first occurrence of venous thromboembolic (VTE) events ; ; 7. Time from randomization to all‐cause mortality Timepoint(s) of evaluation of this end point: Approximately 2 years INCLUSION CRITERIA: ‐ Age =50 ‐ Documented moderate to severe symptomatic lower extremity atherosclerotic peripheral artery disease as evidenced by ALL of the following: a. clinically, by functional limitations in walking activity, ischemic rest pain, or ischemic ulceration, b. anatomically, by imaging evidence of peripheral artery disease distal to the external iliac artery in the index leg within 12 months prior to or at the time of the qualifying revascularization AND c. hemodynamically in either leg (within 12 months prior to, or at the time of, the qualifying revascularization) by: ? an ABI = 0.80 or TBI = 0.60 for patients without a prior history of limb revascularization, OR ? an ABI = 0.85 or TBI = 0.65 for patients with a prior history of limb revascularization; ‐ Technically successful peripheral revascularization distal to the external iliac artery (surgical and/or endovascular; for definition see Section 9.3.3) for symptomat