Efficacy and Safety of Rivaroxaban in Reducing the Risk of Major Thrombotic Vascular Events in Subjects With Symptomatic Peripheral Artery Disease Undergoing Peripheral Revascularization Procedures of the Lower Extremities

Study Overview
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Brief Summary
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The purpose of study was to test whether rivaroxaban added to standard of care treatment, when compared to placebo, had the potential to reduce the incidence of the clinical events related to the clots and complications of the heart and brain (CV death, MI, or stroke) or the legs (acute limb ischemia or major amputation) in patients who had undergone recent procedure(s) to improve the blood flow of their legs.

Official Title
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An International, Multicenter, Randomized, Double-blind, Placebo-controlled Phase 3 Trial Investigating the Efficacy and Safety of Rivaroxaban to Reduce the Risk of Major Thrombotic Vascular Events in Patients With Symptomatic Peripheral Artery Disease Undergoing Lower Extremity Revascularization Procedures

Conditions
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Peripheral Artery Disease

Intervention / Treatment
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* Drug: Rivaroxaban (Xarelto, BAY59-7939)
* Drug: Rivaroxaban-Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥50 Documented moderate to severe symptomatic lower extremity atherosclerotic peripheral artery disease Technically successful peripheral revascularization distal to the external iliac artery for symptomatic PAD (Peripheral artery disease) within the last 10 days prior to randomization Exclusion Criteria: Patients undergoing revascularization for asymptomatic PAD or mild claudication without functional limitation of the index leg. Patients undergoing revascularization of the index leg to treat an asymptomatic or minimally symptomatic restenosis of a bypass graft or target lesion restenosis. Prior revascularization on the index leg within 10 days of the qualifying revascularization. Planned dual antiplatelet therapy (DAPT) use for the qualifying revascularization procedure of clopidogrel in addition to Acetylic salicylic acid (ASA) for >6 months after the qualifying revascularization procedure; it is strongly recommended that any course of clopidogrel is kept to the minimum necessary in accordance with local standard of care and international practice guidelines (typically 30 days, or up to 60 days for some drug-coated products or devices) and is only allowed for up to 6 months for complex procedures or devices in the investigator's opinion that require longer use. Planned use of any additional antiplatelet agent other than clopidogrel and ASA after the qualifying revascularization procedure.

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rivaroxaban<br>Rivaroxaban 2.5 mg orally twice daily (5 mg cumulative daily dose) | Drug: Rivaroxaban (Xarelto, BAY59-7939)<br>* 2.5 mg, twice daily, orally, tablet<br>|
| Placebo Comparator: Placebo<br>Rivaroxaban-placebo orally twice daily | Drug: Rivaroxaban-Placebo<br>* matching placebo, twice daily, orally, tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Efficacy Outcome: Number of Participants With Composite of Myocardial Infarction (MI), Ischemic Stroke, Cardiovascular Death, Acute Limb Ischemia (ALI) and Major Amputation Due to a Vascular Etiology | Only the first occurrence of the outcome event under analysis within the data scope from a participant is considered. | For each participant, the first occurrence of the composite primary efficacy outcome after randomization up until the efficacy cut-off date (08-Sep-2019) was considered. The mean time in follow-up survival time until ECOD that date was 1109.76 days. | 
| Primary Safety Outcome: Number of Participants With TIMI (Thrombolysis in Myocardial Infarction) Major Bleeding | Only the first occurrence of the outcome event under analysis within the data scope from a participant is considered. | For each participant, the first occurrence of the primary safety outcome after randomization up until 2 days after permanent stop of study drug (rivaroxaban or rivaroxaban placebo). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Composite of MI, Ischemic Stroke, Coronary Heart Disease (CHD) Death, ALI, and Major Amputation of a Vascular Etiology | Only the first occurrence of the outcome event under analysis within the data scope from a participant is considered. | For each participant, the first occurrence of the composite efficacy outcome after randomization up until the efficacy cut-off date (08-Sep-2019) was considered. The mean survival time until ECOD was 1108.79 days. | 
| Number of Participants With an Unplanned Index Limb Revascularization for Recurrent Limb Ischemia (Subsequent Index Leg Revascularization That Was Not Planned or Considered as Part of the Initial Treatment Plan at the Time of Randomization) | Only the first occurrence of the outcome event under analysis within the data scope from a participant is considered. | For each participant, the first occurrence of the efficacy outcome after randomization up until the efficacy cut-off date (08-Sep-2019) was considered. The mean survival time until ECOD was 1062.48 days. | 
| Number of Participants With Hospitalization for a Coronary or Peripheral Cause (Either Lower Limb) of a Thrombotic Nature | Only the first occurrence of the outcome event under analysis within the data scope from a participant is considered. | For each participant, the first occurrence of the efficacy outcome after randomization up until the efficacy cut-off date (08-Sep-2019) was considered. The mean survival time until ECOD was 1154.04 days | 
| Number of Participants With Composite of MI, Ischemic Stroke, All-cause Mortality (ACM), ALI, and Major Amputation of a Vascular Etiology | Only the first occurrence of the outcome event under analysis within the data scope from a participant is considered. | For each participant, the first occurrence of the composite efficacy outcome after randomization up until the efficacy cut-off date (08-Sep-2019) was considered. The mean survival time until ECOD was 1085.13 days | 
| Number of Participants With Composite of MI, All-cause Stroke, Cardiovascular (CV) Death, Acute Limb Ischemia (ALI), and Major Amputation of a Vascular Etiology | Only the first occurrence of the outcome event under analysis within the data scope from a participant is considered. | For each participant, the first occurrence of the composite efficacy outcome after randomization up until the efficacy cut-off date (08-Sep-2019) was considered. The mean survival time until ECOD was 1108.29 days | 
| Number of Mortality (All-cause) |  | For each participant, the first occurrence of the outcome after randomization up until the efficacy cut-off date (08-Sep-2019) was considered. The mean survival time until ECOD was 1188.48 days | 
| Number of Participants With Venous Thromboembolic (VTE) Events | Venous thromboembolic events were reported by investigator only. | For each participant, the first occurrence of the outcome after randomization up until the efficacy cut-off date (08-Sep-2019) was considered. The mean survival time until ECOD was 1187.65 days | 
| Secondary Safety Outcome: Number of Participants With ISTH (International Society on Thrombosis and Haemostasis) Major Bleeding | Only the first occurrence of the outcome event under analysis within the data scope from a participant is considered. | For each participant, the first occurrence of the major bleeding events according to the ISTH classification after randomization up until 2 days after permanent stop of study drug (rivaroxaban or rivaroxaban placebo). | 
| Secondary Safety Outcome: Number of Participants With BARC (Bleeding Academic Research Consortium) Type 3b and Above Bleeding Events | Only the first occurrence of the outcome event under analysis within the data scope from a participant is considered | For each participant, the first occurrence of the type 3b and above bleeding events according to the BARC classification after randomization up until 2 days after permanent stop of study drug (rivaroxaban or rivaroxaban placebo) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rivaroxaban, Xarelto, Aspirin, Acetylic salicylic acid, Anticoagulant, Peripheral artery disease, Peripheral arterial disease, Revascularization, Acute limb ischemia, Amputation, Cardiovascular events