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

May 27, 2023 updated by: Seongwook Han, Keimyung University Dongsan Medical Center

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

Recruiting

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

60

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Jongmin Hwang, M.D., Ph.D.
  • Phone Number: +82-53-250-7333
  • Email: dsmcep@dsmc.or.kr

Study Locations

      • Daegu, Korea, Republic of, 41931
        • Recruiting
        • Keimyung University Dongsan Medical Center
        • Contact:
        • Principal Investigator:
          • Seongwook Han, MD, PhD
        • Sub-Investigator:
          • Hyoung-Seob Park, MD
        • Sub-Investigator:
          • Jongmin Hwang, MD, PhD
      • Daegu, Korea, Republic of, 41944
        • Recruiting
        • Division of Cardiology, Department of Internal Medicine, Kyungpook National University Hospital
        • Contact:
          • Myung Hwan Bae, MD, PhD
      • Daegu, Korea, Republic of, 42415
        • Recruiting
        • Division of Cardiology, Department of Internal Medicine, Yeungnam University Hospital
        • Contact:
          • Dong Gu Shin, MD, PhD
      • Daegu, Korea, Republic of, 42472
        • Recruiting
        • Division of Cardiology, Department of Internal Medicine, Daegu Catholic University Medical Center
        • Contact:
          • Young Soo Lee, MD, PhD
      • Incheon, Korea, Republic of, 21431
        • Recruiting
        • Catholic University of Korea, Incheon St. Mary's hospital
        • Contact:
          • Yoori Kim, MD, PhD
      • Pusan, Korea, Republic of, 49241
        • Recruiting
        • Pusan National University Hospital
        • Contact:
          • Jinhee Ahn, MD
      • Seoul, Korea, Republic of, 03080
        • Recruiting
        • Seoul National University Hospital
        • Contact:
          • Eue-Keun Choi, MD, PhD
      • Seoul, Korea, Republic of, 02841
        • Recruiting
        • Korea University Anam Hospital
        • Contact:
          • Jong-Il Choi, MD, PhD
      • Seoul, Korea, Republic of, 03722
        • Recruiting
        • Severance Cardiovascular Hospital
        • Contact:
          • Hui-Nam Pak, MD, PhD
      • Seoul, Korea, Republic of, 06351
        • Recruiting
        • Seoul Samsung Medical Center
        • Contact:
          • Young Keun On, MD, PhD
      • Seoul, Korea, Republic of, 07345
        • Recruiting
        • Catholic University of Korea Yeouido St. Mary's Hospital
        • Contact:
          • Ju-Youn Kim, MD
      • Wŏnju, Korea, Republic of, 26426
        • Recruiting
        • Wonju Severance Christian Hospital
        • Contact:
          • Min-Soo Ahn, MD, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Edoxaban treatment
  1. 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.
  2. Patients in this group are taking Lixiana® (Edoxaban) 60mg for resolution of left atrial appendage thrombi
  3. 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 kg
    • Concomitant use of the following P-glycoprotein (P-gp) inhibitors: ciclosporin,dronedarone, erythromycin, or ketoconazole.
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
Time Frame: 6 weeks
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
Time Frame: 6 weeks
Treatment responses of thrombi: Number of participants with resolved, reduced, unchanged, enlarged thrombi or newly appeared thrombi
6 weeks
Ischemic stroke event
Time Frame: 12 weeks
The percentage of subjects who experienced ischemic stroke
12 weeks
Bleeding event
Time Frame: 12 weeks
The percentage of subjects who experienced bleeding event
12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Study Chair: Seongwook Han, M.D., Ph.D., Keimyung University Dongsan Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 19, 2019

Primary Completion (Estimated)

October 1, 2023

Study Completion (Estimated)

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)

May 31, 2023

Last Update Submitted That Met QC Criteria

May 27, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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