A Trial of Rivaroxaban Versus Warfarin in Dissolving Left Atrial Appendage Thrombus in Patients With Atrial Fibrillation

Study Overview
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Brief Summary
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The purpose of this clinical randomized trial is to evaluate the efficacy and safety of rivaroxaban compared with warfarin in dissolving the LAA thrombus in patients with atrial fibrillation.

Detailed Description
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Left atrial appendage (LAA) thrombosis is a common complication of atrial fibrillation and will significantly increase the incidence of stroke in patients. Warfarin is a classical oral anticoagulant which can dissolve thrombus, but its clinical use has many limitations and it requires strict monitoring of coagulation. Recently, some studies have shown that NOAC (dabigatran / rivaroxaban) can dissolve left atrial appendage thrombosis. The application of rivaroxaban in the X-TRA study dissolved 41.5% of LAA thrombus after 6 weeks, indicating its potential clinical application prospects. Whether rivaroxaban is not inferior to warfarin for rapid dissolution of LAA thrombus, there is no prospective randomized controlled trial.

Official Title
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A Prospective Randomized Controlled Trial of Rivaroxaban Versus Warfarin in Dissolving Left Atrial Appendage Thrombus in Patients With Atrial Fibrillation

Conditions
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Atrial Fibrillation, Left Atrial Appendage Thrombosis, Rivaroxaban

Intervention / Treatment
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* Drug: Rivaroxaban
* Drug: Warfarin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Get informed consent from the patient or family. Non-valvular atrial fibrillation / atrial flutter. The first transesophageal echocardiogram revealed a left atrial appendage thrombus (within 7 days of detection of thrombus). Age at 18-80 years old. CrCL≥ 30 mL/min (Cockcroft-Gault). AST/ALT is less than 2 times the upper limit of normal. Women of childbearing age need contraception. Exclusion Criteria: Pregnant or lactating woman. Can't understand or follow the research plan. Patients under 18 or over 80 years old. Low weight (< 40 kg). Previously found LAA thrombus and have taken anticoagulant drugs. Patients with contraindications for anticoagulation. Patients who need to use antiplatelet drugs simultaneously within 6-12 months after ACS or PCI. A history of cerebral hemorrhage. Patients with active bleeding. Severe gastritis, gastroesophageal reflux patients. Combination of P-glycoprotein inhibitors and other drugs in the presence of NOAC contraindications. 13.Patient with tumor. 14.Planned surgery within 3 months. 15.Other investigators believe that patients are not suitable for enrollment.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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
Interventional Model Description: two groups, group one is for Rivaroxaban 20mg qd (15mg qd If creatinine clearance is between 30-49ml/min), group two is for warfarin, keep the INR between 2-3.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: rivaroxaban<br>After diagnosis of left atrial appendage thrombus by transesophageal echocardiography, then start with rivaroxaba 20mg qd(15mg If creatinine clearance is between 30-49 ml/min ). | Drug: Rivaroxaban<br>* After diagnosis of left atrial appendage thrombus by transesophageal echocardiography, then start with rivaroxaba 20mg qd (15mg If creatinine clearance is between 30-49 ml/min).<br>|
| Active Comparator: Warfarin<br>After diagnosis of left atrial appendage thrombus by transesophageal echocardiography, subcutaneous injection of low molecular weight heparin and oral warfarin treatment were started, and low molecular weight heparin was stopped after INR reached 2. | Drug: Warfarin<br>* After the diagnosis of left atrial appendage thrombus by transesophageal echocardiography, subcutaneous injection of low molecular weight heparin (4000iu q12h) and oral warfarin treatment were started, and low molecular weight heparin was stopped after INR reached 2.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patient who's thrombus in the left atrium or left atrial appendage is completely dissolved within 3 to 6 weeks | Transesophageal echocardiography was used to assess whether there was a left atrial appendage thrombus at 3rd, 6th week after initiation of anticoagulant therapy. | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patient who's thrombus in the left atrium or left atrial appendage is completely dissolved within 12 weeks | Transesophageal echocardiography was used to assess whether there was a left atrial appendage thrombus at 12th week after initiation of anticoagulant therapy. | 12 weeks | 
| Size change of left atrial appendage or left atrium thrombus | If a left atrial appendage or left atrial thrombus is detected,then the size of the thrombus is measured using echocardiography。 | 12 weeks | 
| Number of severe bleeding cases such as gastrointestinal bleeding and cerebral hemorrhage. | Number of severe bleeding cases such as gastrointestinal bleeding and cerebral hemorrhage. | 12 weeks | 
| Number of transient ischemic attacks (TIA) and strokes | Number of transient ischemic attacks (TIA) and strokes | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Atrial Fibrillation, Left Atrial Appendage Thrombosis, rivaroxaban