Exploring the Efficacy of Once Daily Oral Rivaroxaban for Treatment of Thrombus in Left Atrial/Left Atrial Appendage in Subjects With Nonvalvular Atrial Fibrillation or Atrial Flutter

Study Overview
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Brief Summary
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A study for subjects with atrial fibrillation (AF) or atrial flutter who are diagnosed with left atrial (LA) or left atrial appendage (LAA) thrombus. The study will assign subjects to rivaroxaban for treatment of thrombi. The study will measure thrombus outcomes based on echo image and common clinical outcomes such as bleeding and stroke or thromboembolism.

Official Title
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An Open-label, International, Multicenter, Interventional Study Exploring the Efficacy of Once-daily Oral Rivaroxaban (BAY 59-7939) for the Treatment of Left Atrial/Left Atrial Appendage Thrombus in Subjects With Nonvalvular Atrial Fibrillation or Atrial Flutter

Conditions
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Atrial Fibrillation

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men or women aged >/= 18 years Hemodynamically stable nonvalvular AF or atrial flutter LA/LAA thrombus documented at baseline by transesophageal echocardiography (TEE) up to 72 hours prior to start of study medication vitamin K antagonist(s) (VKA)/ new oral anticoagulant(s) (NOAC)-naïve or untreated within 1 month prior to signing of the informed consent form VKA pretreated but under ineffective INR levels(<2.0,documented with at least 2 consecutive measurements that are at least 24 hours apart) within last 6 weeks Women of childbearing potential and men must agree to use adequate contraception when sexually active Exclusion Criteria: Transient Ischemic Attack within 3 days prior to study inclusion Severe, disabling stroke (modified Rankin score of 4-5, inclusive) within 3 months or any stroke within 14 days before the start of study drug Acute thromboembolic events or thrombosis (venous/arterial) within the last 14 days prior to study inclusion Acute myocardial infarction within the last 14 days prior to study inclusion Cardiac-related criteria: Previous intracardiac thrombus, Free-floating ball thrombus, Intracardiac tumor, known left ventricular or aortic thrombus Active bleeding or high risk for bleeding contraindicating anticoagulant therapy Concomitant drugs/therapies: Indication for anticoagulant therapy for a condition other than nonvalvular AF or atrial flutter (eg, venous thromboembolism). Concomitant use of anticoagulant drugs, including VKA, or factor IIa or factor Xa inhibitors. Chronic aspirin therapy >100 mg or dual antiplatelet therapy. Concomitant use of strong inhibitors of both cytochrome P450 (CYP) 3A4 and P glycoprotein (P-gp), ie, all human immunodeficiency virus protease inhibitors and the following azole antimycotics agents-ketoconazole, itraconazole, voriconazole, and posaconazole-if used systemically Concomitant conditions: Childbearing potential without proper contraceptive measures, pregnancy, or breast feeding. Hypersensitivity to investigational treatment. Calculated creatinine clearance (CrCl) < 15 mL/minute at the screening visit. Hepatic disease which is associated with coagulopathy leading to a clinically relevant bleeding risk. Any severe condition that would limit life expectancy to less than 3 months (eg, advanced malignancy, etc.). Planned invasive procedure with potential for uncontrolled bleeding or increased risk of stroke, including major surgery, cardiac catheterization, or cardioversion prior to the end-of-treatment TEE. Inability to take oral medication. Ongoing drug addiction or alcohol abuse

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rivaroxaban<br> | Drug: Rivaroxaban (Xarelto, BAY59-7939)<br>* Rivaroxaban 20 mg orally once daily for 6 weeks; subjects with severe to moderate renal impairment (ie, CrCl of 15 to 49 mL/min, inclusive) will receive the adjusted dose of 15 mg orally once daily for 6 weeks in the study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The percentage of subjects with complete resolution of left atrial or left atrial appendage thrombus at the end of treatment | Complete resolution is characterized as the subject is completely thrombus-free confirmed on transesophageal echocardiography | After 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Categories of thrombus outcome in subjects: resolved, reduced, unchanged, enlarged or new |  | After 6 weeks | 
| The composite number of stroke and non-central nervous system systemic embolism events |  | Up to 12 weeks | 
| The number of all bleeding events |  | Up to 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rivaroxaban, Oral anticoagulant, Nonvalvular atrial fibrillation, Left atrial thrombus, Transesophageal echocardiography, Thrombus resolution, Stroke, Thromboembolism