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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Atrial Fibrillation; Left Atrial Appendage Thrombosis; Rivaroxaban
• Intervention / Treatment: Drug: Rivaroxaban; Drug: Warfarin

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: YANPING XU; Phone Number: +86-023-63693079

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Get informed consent from the patient or family.
2. Non-valvular atrial fibrillation / atrial flutter.
3. The first transesophageal echocardiogram revealed a left atrial appendage thrombus (within 7 days of detection of thrombus).
4. Age at 18-80 years old.
5. CrCL≥ 30 mL/min (Cockcroft-Gault).
6. AST/ALT is less than 2 times the upper limit of normal.
7. Women of childbearing age need contraception.

Exclusion Criteria:

1. Pregnant or lactating woman.
2. Can't understand or follow the research plan.
3. Patients under 18 or over 80 years old.
4. Low weight (< 40 kg).
5. Previously found LAA thrombus and have taken anticoagulant drugs.
6. Patients with contraindications for anticoagulation.
7. Patients who need to use antiplatelet drugs simultaneously within 6-12 months after ACS or PCI.
8. A history of cerebral hemorrhage.
9. Patients with active bleeding.
10. Severe gastritis, gastroesophageal reflux patients.
11. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: rivaroxaban; 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; 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).
Active Comparator: Warfarin; 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; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: The Second Affiliated Hospital of Chongqing Medical University

Publications and helpful links

General Publications

• Lip GY, Hammerstingl C, Marin F, Cappato R, Meng IL, Kirsch B, van Eickels M, Cohen A; X-TRA study and CLOT-AF registry investigators. Left atrial thrombus resolution in atrial fibrillation or flutter: Results of a prospective study with rivaroxaban (X-TRA) and a retrospective observational registry providing baseline data (CLOT-AF). Am Heart J. 2016 Aug;178:126-34. doi: 10.1016/j.ahj.2016.05.007. Epub 2016 May 17.

Study record dates

Study Major Dates

• Study Start (Anticipated): June 1, 2019
• Primary Completion (Anticipated): January 1, 2022
• Study Completion (Anticipated): December 30, 2022

Study Registration Dates

• First Submitted: December 31, 2018
• First Submitted That Met QC Criteria: December 31, 2018
• First Posted (Actual): January 3, 2019

Study Record Updates

• Last Update Posted (Actual): March 19, 2019
• Last Update Submitted That Met QC Criteria: March 18, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: Atrial Fibrillation; rivaroxaban; Left Atrial Appendage Thrombosis
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Arrhythmias, Cardiac; Atrial Fibrillation; Thrombosis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Rivaroxaban; Warfarin
• Other Study ID Numbers: REVIEW-AF

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No