Global Study Comparing a rivAroxaban-based Antithrombotic Strategy to an antipLatelet-based Strategy After Transcatheter aortIc vaLve rEplacement to Optimize Clinical Outcomes
- Conditions
- Transcatheter Aortic Valve Replacement
- Interventions
- Drug: Acetylsalicylic Acid (ASA)
- Registration Number
- NCT02556203
- Lead Sponsor
- Bayer
- Brief Summary
To assess whether a rivaroxaban-based anticoagulation strategy, following successful TAVR, compared to an antiplatelet-based strategy, is superior in reducing death or first thromboembolic events (DTE).
To assess the primary bleeding events (PBE) of the rivaroxaban-based strategy compared to an antiplatelet-based strategy, following TAVR.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 1653
-
Successful TAVR (Transcatheter Aortic Valve Replacement) of an aortic valve stenosis (either native or valve-in-valve)
- By iliofemoral or subclavian access
- With any approved/marketed device
- Atrial fibrillation (AF), current or previous, with an ongoing indication for oral anticoagulant treatment
- Any other indication for continued treatment with any oral anticoagulant (OAC)
- Known bleeding diathesis (such as but not limited to active internal bleeding, clinically significant bleeding, platelet count ≤ 50,000/mm3 at screening, hemoglobin level < 8.5 g/dL, active peptic ulcer or known gastrointestinal (GI) bleeding, history of intracranial hemorrhage or subdural hematoma)
- Any ongoing absolute indication for dual antiplatelet therapy (DAPT) at time of screening that is unrelated to the TAVR procedure
- Clinically overt stroke within the last 3 months
- Planned coronary or vascular intervention or major surgery
- Severe renal impairment (eGFR < 30 mL/min/1.73 m2) or on dialysis, or post-TAVR unresolved acute kidney injury with renal dysfunction stage 2 or higher
- Moderate and severe hepatic impairment (Child-Pugh Class B or C) or any hepatic disease associated with coagulopathy
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Rivaroxaban (Xarelto, BAY59-7939) Rivaroxaban (Xarelto, BAY59-7939) Subjects were treated with Rivaroxaban (10mg once-daily) and ASA (75-100mg once-daily) within first 90 days after randomization. After 90 days, ASA was discontinued and rivaroxaban (10mg once-daily) was to be continued alone. In the event of NOAF (New Onset of Atrial Fibrillation), subjects should be switched to rivaroxaban (20/15mg once-daily) and ASA (75-100mg once-daily) within first 90 days. After 90 days, ASA was discontinued and rivaroxaban (20/15mg once-daily) was to be continued alone. Rivaroxaban (Xarelto, BAY59-7939) Acetylsalicylic Acid (ASA) Subjects were treated with Rivaroxaban (10mg once-daily) and ASA (75-100mg once-daily) within first 90 days after randomization. After 90 days, ASA was discontinued and rivaroxaban (10mg once-daily) was to be continued alone. In the event of NOAF (New Onset of Atrial Fibrillation), subjects should be switched to rivaroxaban (20/15mg once-daily) and ASA (75-100mg once-daily) within first 90 days. After 90 days, ASA was discontinued and rivaroxaban (20/15mg once-daily) was to be continued alone. Antiplatelet Acetylsalicylic Acid (ASA) Subjects were treated with clopidogrel (75mg once-daily) and ASA (75-100mg once-daily) within first 90 days after randomization. After 90 days, clopidogrel was discontinued and ASA (75-100mg once-daily) was to be continued alone. In the event of NOAF, subjects should start treatment of open-label VKA to target INR 2 to 3 (according to guidelines) and ASA (75-100mg once-daily) within first 90 days. After 90 days, ASA was discontinued and VKA was to be continued alone. Antiplatelet Vitamin K antagonist (VKA) Subjects were treated with clopidogrel (75mg once-daily) and ASA (75-100mg once-daily) within first 90 days after randomization. After 90 days, clopidogrel was discontinued and ASA (75-100mg once-daily) was to be continued alone. In the event of NOAF, subjects should start treatment of open-label VKA to target INR 2 to 3 (according to guidelines) and ASA (75-100mg once-daily) within first 90 days. After 90 days, ASA was discontinued and VKA was to be continued alone. Antiplatelet Clopidogrel Subjects were treated with clopidogrel (75mg once-daily) and ASA (75-100mg once-daily) within first 90 days after randomization. After 90 days, clopidogrel was discontinued and ASA (75-100mg once-daily) was to be continued alone. In the event of NOAF, subjects should start treatment of open-label VKA to target INR 2 to 3 (according to guidelines) and ASA (75-100mg once-daily) within first 90 days. After 90 days, ASA was discontinued and VKA was to be continued alone.
- Primary Outcome Measures
Name Time Method Number of Participants With Death or First Thromboembolic Event (DTE) Through study completion, on average 16 months Death or first adjudicated thromboembolic event (DTE), defined as composite of all-cause death, any stroke, myocardial infarction (MI), symptomatic valve thrombosis, pulmonary embolism (PE), deep vein thrombosis (DVT), and non-central nervous system (CNS) systemic embolism.
Number of Participants With Primary Bleeding Event (PBE) Through study completion, on average 16 months PBE is defined according to VARC (Valve Academic Research Consortium) definitions as the adjudicated composite of: Life-threatening, disabling or major bleeding.
- Secondary Outcome Measures
Name Time Method Number of Participants With Cardiovascular Death or Thromboembolic Event Through study completion, on average 16 months Composite of CV-death, any stroke, myocardial infarction (MI), symptomatic valve thrombosis, pulmonary embolism (PE), deep vein thrombosis (DVT), and non-central nervous system (CNS) systemic embolism (per adjudication).
Number of Participants With Composite Bleeding Endpoint of BARC (Bleeding Academic Research Consortium) 2, 3, or 5 Bleeds Through study completion, on average 16 months Composite of BARC 2,3 or 5 bleedings
Number of Participants With Net-clinical Benefit Through study completion, on average 16 months The net-clinical-benefit defined as the adjudicated composite of all-cause death, any stroke, myocardial infarction, symptomatic valve thrombosis, pulmonary embolism, deep vein thrombosis, non-CNS systemic embolism (efficacy); VARC life-threatening, disabling and VARC major bleeds (safety).
Number of Participants With TIMI (Thrombolysis In Myocardial Infarction) Major / Minor Bleeds Through study completion, on average 16 months Composite of TIMI major and minor bleedings
Number of Participants With ISTH (International Society on Thrombosis and Haemostasis) Major Bleeds Through study completion, on average 16 months ISTH major bleeds