A Study Exploring Two Treatment Strategies in Patients With Atrial Fibrillation Who Undergo Catheter Ablation Therapy

Study Overview
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Brief Summary
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The purpose of this exploratory study is to evaluate the safety of rivaroxaban and uninterrupted vitamin K antagonist (VKA) in adult participants with non-valvular atrial fibrillation (NVAF) who undergo catheter ablation as measured by post-procedure major bleeding events.

Detailed Description
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This is a randomized (participants are assigned to intervention groups by chance), open-label (both physicians and participants know the identity of the assigned treatment), active-controlled, multi-center safety study of rivaroxaban or VKA before and after a catheter ablation procedure. This study requires collaboration with medical institutions that provide access to electrophysiologists who normally perform the catheter ablation procedure. In this study, NVAF is to be defined as the presence of AF in a person who does not have a prosthetic heart valve (annuloplasty with or without prosthetic ring, commissurotomy and/or valvuloplasty are permitted) and who does not have hemodynamically significant mitral valve stenosis. Approximately 250 eligible participants, age 18 years or older, with a history of paroxysmal, persistent, or long standing persistent NVAF who are scheduled to undergo an elective catheter ablation procedure will be randomized in a 1:1 ratio to receive either rivaroxaban 20 mg orally, once-daily, administered preferably with the evening meal or VKA (adjusted to achieve a recommended International Normalized Ratio of 2.0 to 3.0). The study will consist of a screening period, a pre-procedure period, procedure period and post-procedure period. The screening period will begin up to 2 weeks prior to randomization. Participants will be randomized at the beginning of the pre-procedure period. During this period, participants will be recommended to receive their assigned treatment for at least 4 weeks (maximum of 5 weeks) before the catheter ablation procedure. For participants with the sufficient anticoagulation, documented for the 3 weeks prior to randomization, and for participants with a transesophageal echocardiogram (TEE) or intracardiac echocardiography (ICE), the length of the pre-procedure period may be reduced down to 1-7 days and must include any transition from the previous anticoagulation therapy to randomized study drug. After the catheter ablation procedure, participants will receive their post-procedure dose of study drug through a minimum of 30 + - 5 days. In addition to scheduled visits and telephone calls the study may also include additional phone calls and visits by the participant to the site when dose adjustment is required for usual care.

Official Title
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A Randomized, Open-label, Active-controlled Multi-center Study to Assess Safety of Uninterrupted Rivaroxaban vs. Usual Care in Subjects Undergoing Catheter Ablation Therapy for Atrial Fibrillation

Conditions
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Atrial Fibrillation

Intervention / Treatment
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* Drug: rivaroxaban
* Drug: uninterrupted vitamin K antagonist (VKA)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be scheduled for a catheter ablation procedure for non-valvular atrial fibrillation (NVAF); Have a documented history of paroxysmal (lasting <1 week) or persistent (lasting >1 week and <1 year or requiring pharmacological or electrical cardioversion), or long standing persistent (>=1 year) NVAF; Be suitable for anticoagulant therapy and catheter ablation as per the judgment of the investigator; Women must be postmenopausal before entry or practicing a highly effective method of birth control when heterosexually active; Women of childbearing potential must have a negative serum pregnancy test at screening; Be willing and able to adhere to the prohibitions and restrictions specified in the study protocol; Have a life expectancy of at least 6 months Exclusion Criteria: Has a history of a prior stroke, transient ischemic attack (TIA) or non-convulsive status epilepticus within 6 months of the screening visit; Has a history of a major bleeding or thromboembolic event within the 12 months immediately preceding the catheter ablation procedure; Has had major surgery (requiring general anesthesia), within 6 months before screening or planned surgery during the time the subject is expected to participate in the study; Has NVAF due to electrolyte imbalance, hyperthyroidism, or other reversible or noncardiac cause of NVAF; Has any condition that, in the opinion of the investigator, would make participation not be in the best interest (eg, compromise the well-being) of the participant or that could prevent, limit, or confound the protocol-specified assessments

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: rivaroxaban<br>rivaroxaban 20 mg orally, once-daily, administered preferably with the evening meal | Drug: rivaroxaban<br>* rivaroxaban 20 mg orally, once-daily, administered preferably with the evening meal<br>|
| Experimental: vitamin K antagonist (VKA)<br>dose-adjusted vitamin K antagonist (VKA) to achieve a recommended International Normalized Ratio (INR) of 2.0 to 3.0 | Drug: uninterrupted vitamin K antagonist (VKA)<br>* dose-adjusted vitamin K antagonist (VKA) to achieve a recommended International Normalized Ratio (INR) of 2.0 to 3.0<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Incidence of Post-Procedure Major Bleeding Events | Post-procedure major bleeding events include Thrombolysis in Myocardial Infarction (TIMI), International Society on Thrombosis and Haemostasis (ISTH) and Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) Severe/life threatening bleeding. | Up to 30 plus or minus (+-) 5 days after the catheter ablation procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Composite Endpoint of Myocardial Infarction (MI), Ischemic Stroke, Non-Central Nervous System (Non-CNS) Systemic Embolism and Vascular Death | The composite endpoint include Myocardial Infarction (MI), Ischemic Stroke, Non-Central Nervous System (non-CNS) Systemic Embolism and Vascular Death. | Up to 30 plus or minus (+-) 5 days after the catheter ablation procedure | 
| Number of Participants With Myocardial Infarction (MI) | The MI was defined as clinical symptoms consistent with myocardial ischemia and cardiac biomarker elevation greater than the site's upper limit of normal (ULN) or development of new pathological Q waves in at least 2 contiguous leads on the electrocardiogram (ECG) or autopsy confirmation, OR Creatine kinase-muscle and brain subunit [or creatine kinase (CK) in the absence of CK-MB] greater than (>) 3 or 5 or 10 x ULN for samples obtained within 24 hours of the procedure if the baseline values were normal or at least a 50 percent (%) increase over elevated baseline values that were stable or decreasing or development of new pathological Q waves in at least 2 contiguous leads on the electrocardiogram. Symptoms of cardiac ischemia were not required. | Up to 30 plus or minus (+-) 5 days after the catheter ablation procedure | 
| Number of Participants With Ischemic Stroke | Stroke was defined as a new, sudden, focal neurological deficit resulting from a presumed cerebrovascular cause that was not reversible within 24 hours and not due to a readily identifiable cause such as a tumor or seizure. | Up to 30 plus or minus (+-) 5 days after the catheter ablation procedure | 
| Number of Participants With Non-Central Nervous System (Non-CNS) Systemic Embolism | The Non-CNS systemic embolism was defined as abrupt vascular insufficiency associated with clinical or radiological evidence of arterial occlusion in the absence of other likely mechanisms, (example; trauma, atherosclerosis, instrumentation). | Up to 30 plus or minus (+-) 5 days after the catheter ablation procedure | 
| Number of Participants With Vascular Death | Any death that was not clearly non-vascular. Examples of vascular death included deaths due to bleeding, Myocardial Infarction (MI), stroke, heart failure and arrhythmias. | Up to 30 plus or minus (+-) 5 days after the catheter ablation procedure | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Atrial Fibrillation, Irregular heart beat, Catheter Ablation, Rivaroxaban