Resolution of Thrombi in Left Atrial Appendage With Edoxaban (REFLEX)

Non-valvular (NV) atrial fibrillation (AF) increases the risk of stroke by approximately fivefold. The atrial thrombi associated with AF are seen within the left atrial appendage (LAA) in most cases (> 90%). Anticoagulation with a vitamin-K antagonist (VKA) is recommended to prevent thromboembolic complications and to resolve thrombi. Non-VKA oral anticoagulants (NOACs) have replaced the VKA for the thromboprophylaxis in patients with NVAF since 2010. Therefore, NOAC can be the excellent alternative to VKA concerning resolving preexisting LAA thrombi because of its rapid onset of action and no need of bridging with heparin. However, there is still lack of data regarding the optimal treatment for patients with AF and thrombi in LAA with NOAC. There are only several case reports of the efficacy of NOACs in resolving LAA thrombi available.

Edoxaban, which has data showing efficacy and safety in thromboprophylaxis, can be the new option for treatment of patients with AF and LAA thrombi. The purpose of this study is to evaluate the efficacy of Edoxaban in resolving the LAA thrombi, which is related with nonvalvular AF.

Study Overview

• Status: Completed
• Conditions: Atrial Fibrillation; Left Atrial Appendage Thrombosis
• Intervention / Treatment: Drug: Edoxaban

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Daegu, Korea, Republic of, 41931
    • Keimyung University Dongsan Medical Center
  • Daegu, Korea, Republic of, 41944
    • Division of Cardiology, Department of Internal Medicine, Kyungpook National University Hospital
  • Daegu, Korea, Republic of, 42415
    • Division of Cardiology, Department of Internal Medicine, Yeungnam University Hospital
  • Daegu, Korea, Republic of, 42472
    • Division of Cardiology, Department of Internal Medicine, Daegu Catholic University Medical Center
  • Incheon, Korea, Republic of, 21431
    • Catholic University of Korea, Incheon ST. Mary's Hospital
  • Pusan, Korea, Republic of, 49241
    • Pusan National University Hospital
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 02841
    • Korea University Anam Hospital
  • Seoul, Korea, Republic of, 03722
    • Severance Cardiovascular Hospital
  • Seoul, Korea, Republic of, 06351
    • Seoul Samsung Medical Center
  • Seoul, Korea, Republic of, 07345
    • Catholic University of Korea Yeouido St. Mary's Hospital
  • Wŏnju, Korea, Republic of, 26426
    • WonJu Severance Christian Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Men or women aged ≥ 20 years
• Hemodynamically stable nonvalvular AF or atrial flutter
• LAA thrombus documented by TEE up to 72 hours prior to start of study medication
• VKA or NOAC-naïve or untreated within 1 month prior to sign the informed consent
• VKA pretreated but under the therapeutic International Normalized ratio 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Edoxaban treatment; Men or women aged ≥ 20 years with NVAF patients who has LAA thrombi documented by transesophageal echocardiography (TEE) up to 72 hours prior to start of study medication are eligible.; Patients in this group are taking Lixiana® (Edoxaban) 60mg for resolution of left atrial appendage thrombi; Reduced (30mg) dose is administered in patients with one or more of the following clinical factors:Moderate or severe renal impairment (creatinine clearance (CrCL) 15 - 50 mL/min)Low body weight ≤ 60 kgConcomitant use of the following P-glycoprotein (P-gp) inhibitors: ciclosporin,dronedarone, erythromycin, or ketoconazole.

Drug: Edoxaban; Edoxaban will be used for resolution of left atrial appendage thrombi; Other Names: Lixiana®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
complete resolution of LAA thrombi	The percentage of subjects with complete resolution of LAA thrombi	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment responses of thrombi	Treatment responses of thrombi: Number of participants with resolved, reduced, unchanged, enlarged thrombi or newly appeared thrombi	6 weeks
Ischemic stroke event	The percentage of subjects who experienced ischemic stroke	12 weeks
Bleeding event	The percentage of subjects who experienced bleeding event	12 weeks

Collaborators and Investigators

• Sponsor: Keimyung University Dongsan Medical Center
• Collaborators: Daiichi Sankyo Korea Co., Ltd., a Daiichi Sankyo Company
• Investigators: Study Chair: Seongwook Han, M.D., Ph.D., Keimyung University Dongsan Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): May 19, 2019
• Primary Completion (Actual): October 30, 2023
• Study Completion (Actual): August 1, 2024

Study Registration Dates

• First Submitted: February 11, 2019
• First Submitted That Met QC Criteria: February 11, 2019
• First Posted (Actual): February 15, 2019

Study Record Updates

• Last Update Posted (Actual): August 19, 2024
• Last Update Submitted That Met QC Criteria: August 16, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• 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; Edoxaban
• Other Study ID Numbers: 2018-09-041

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No