Global Study Comparing a rivAroxaban-based Antithrombotic Strategy to an antipLatelet-based Strategy After Transcatheter aortIc vaLve rEplacement to Optimize Clinical Outcomes

Study Overview
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Brief Summary
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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.

Official Title
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Global Multicenter, Open-label, Randomized, Event-driven, Active-controlled Study Comparing a rivAroxaban-based Antithrombotic Strategy to an antipLatelet-based Strategy After Transcatheter aortIc vaLve rEplacement (TAVR) to Optimize Clinical Outcomes

Conditions
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Transcatheter Aortic Valve Replacement

Intervention / Treatment
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* Drug: Rivaroxaban (Xarelto, BAY59-7939)
* Drug: Acetylsalicylic Acid (ASA)
* Drug: Clopidogrel
* Drug: Rivaroxaban (Xarelto, BAY59-7939)
* Drug: Vitamin K antagonist (VKA)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rivaroxaban (Xarelto, BAY59-7939)<br>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. | Drug: Rivaroxaban (Xarelto, BAY59-7939)<br>* 10mg OD (once-daily)<br>Drug: Acetylsalicylic Acid (ASA)<br>* 75-100mg OD<br>Drug: Rivaroxaban (Xarelto, BAY59-7939)<br>* In case of NOAF, 20/15 mg OD (once-daily)<br>|
| Active Comparator: Antiplatelet<br>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. | Drug: Acetylsalicylic Acid (ASA)<br>* 75-100mg OD<br>Drug: Clopidogrel<br>* 75mg OD<br>Drug: Vitamin K antagonist (VKA)<br>* In case of NOAF, Open-label VKA therapy to target international normalized ratio (INR) 2-3, according to guidelines<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Death or First Thromboembolic Event (DTE) | 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. | Through study completion, on average 14 months | 
| Number of Participants With Death or First Thromboembolic Event (DTE) | 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. | Through study completion, on average 16 months | 
| Number of Participants With Primary Bleeding Event (PBE) | PBE is defined according to VARC (Valve Academic Research Consortium) definitions as the adjudicated composite of: Life-threatening, disabling or major bleeding. | Through study completion, on average 16 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Net-clinical Benefit | 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). | Through study completion, on average 16 months | 
| Number of Participants With Cardiovascular Death or Thromboembolic Event | 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). | Through study completion, on average 16 months | 
| Number of Participants With TIMI (Thrombolysis In Myocardial Infarction) Major / Minor Bleeds | Composite of TIMI major and minor bleedings | Through study completion, on average 16 months | 
| Number of Participants With ISTH (International Society on Thrombosis and Haemostasis) Major Bleeds | ISTH major bleeds | Through study completion, on average 16 months | 
| Number of Participants With Composite Bleeding Endpoint of BARC (Bleeding Academic Research Consortium) 2, 3, or 5 Bleeds | Composite of BARC 2,3 or 5 bleedings | Through study completion, on average 16 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TAVR, TAVI, Transfemoral aortic valve implantation