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

Primary Purpose

Atrial Fibrillation, Left Atrial Appendage Thrombosis

Status
Recruiting
Phase
Phase 4
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Edoxaban
Sponsored by
Keimyung University Dongsan Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Atrial Fibrillation

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Keimyung University Dongsan Medical CenterRecruiting
  • Division of Cardiology, Department of Internal Medicine, Kyungpook National University HospitalRecruiting
  • Division of Cardiology, Department of Internal Medicine, Yeungnam University HospitalRecruiting
  • Division of Cardiology, Department of Internal Medicine, Daegu Catholic University Medical CenterRecruiting
  • Catholic University of Korea, Incheon St. Mary's hospitalRecruiting
  • Pusan National University HospitalRecruiting
  • Korea University Anam HospitalRecruiting
  • Seoul National University HospitalRecruiting
  • Severance Cardiovascular HospitalRecruiting
  • Seoul Samsung Medical CenterRecruiting
  • Catholic University of Korea Yeouido St. Mary's HospitalRecruiting
  • Wonju Severance Christian HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Edoxaban treatment

Arm Description

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 kg Concomitant use of the following P-glycoprotein (P-gp) inhibitors: ciclosporin,dronedarone, erythromycin, or ketoconazole.

Outcomes

Primary Outcome Measures

complete resolution of LAA thrombi
The percentage of subjects with complete resolution of LAA thrombi

Secondary Outcome Measures

Treatment responses of thrombi
Treatment responses of thrombi: Number of participants with resolved, reduced, unchanged, enlarged thrombi or newly appeared thrombi
Ischemic stroke event
The percentage of subjects who experienced ischemic stroke
Bleeding event
The percentage of subjects who experienced bleeding event

Full Information

First Posted
February 11, 2019
Last Updated
May 27, 2023
Sponsor
Keimyung University Dongsan Medical Center
Collaborators
Daiichi Sankyo Korea Co., Ltd., a Daiichi Sankyo Company
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1. Study Identification

Unique Protocol Identification Number
NCT03840291
Brief Title
Resolution of Thrombi in Left Atrial Appendage With Edoxaban
Acronym
REFLEX
Official Title
Resolution of Thrombi in Left Atrial Appendage With Edoxaban
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 19, 2019 (Actual)
Primary Completion Date
October 2023 (Anticipated)
Study Completion Date
August 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Keimyung University Dongsan Medical Center
Collaborators
Daiichi Sankyo Korea Co., Ltd., a Daiichi Sankyo Company

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Atrial Fibrillation, Left Atrial Appendage Thrombosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Edoxaban treatment
Arm Type
Experimental
Arm Description
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 kg Concomitant use of the following P-glycoprotein (P-gp) inhibitors: ciclosporin,dronedarone, erythromycin, or ketoconazole.
Intervention Type
Drug
Intervention Name(s)
Edoxaban
Other Intervention Name(s)
Lixiana®
Intervention Description
Edoxaban will be used for resolution of left atrial appendage thrombi
Primary Outcome Measure Information:
Title
complete resolution of LAA thrombi
Description
The percentage of subjects with complete resolution of LAA thrombi
Time Frame
6 weeks
Secondary Outcome Measure Information:
Title
Treatment responses of thrombi
Description
Treatment responses of thrombi: Number of participants with resolved, reduced, unchanged, enlarged thrombi or newly appeared thrombi
Time Frame
6 weeks
Title
Ischemic stroke event
Description
The percentage of subjects who experienced ischemic stroke
Time Frame
12 weeks
Title
Bleeding event
Description
The percentage of subjects who experienced bleeding event
Time Frame
12 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jongmin Hwang, M.D., Ph.D.
Phone
+82-53-250-7333
Email
dsmcep@dsmc.or.kr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Seongwook Han, M.D., Ph.D.
Organizational Affiliation
Keimyung University Dongsan Medical Center
Official's Role
Study Chair
Facility Information:
Facility Name
Keimyung University Dongsan Medical Center
City
Daegu
ZIP/Postal Code
41931
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jongmin Hwang, M.D.
Phone
+82-53-250-7333
Email
dsmcep@dsmc.or.kr
First Name & Middle Initial & Last Name & Degree
Seongwook Han, MD, PhD
First Name & Middle Initial & Last Name & Degree
Hyoung-Seob Park, MD
First Name & Middle Initial & Last Name & Degree
Jongmin Hwang, MD, PhD
Facility Name
Division of Cardiology, Department of Internal Medicine, Kyungpook National University Hospital
City
Daegu
ZIP/Postal Code
41944
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Myung Hwan Bae, MD, PhD
Facility Name
Division of Cardiology, Department of Internal Medicine, Yeungnam University Hospital
City
Daegu
ZIP/Postal Code
42415
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dong Gu Shin, MD, PhD
Facility Name
Division of Cardiology, Department of Internal Medicine, Daegu Catholic University Medical Center
City
Daegu
ZIP/Postal Code
42472
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Young Soo Lee, MD, PhD
Facility Name
Catholic University of Korea, Incheon St. Mary's hospital
City
Incheon
ZIP/Postal Code
21431
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yoori Kim, MD, PhD
Facility Name
Pusan National University Hospital
City
Pusan
ZIP/Postal Code
49241
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jinhee Ahn, MD
Facility Name
Korea University Anam Hospital
City
Seoul
ZIP/Postal Code
02841
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jong-Il Choi, MD, PhD
Facility Name
Seoul National University Hospital
City
Seoul
ZIP/Postal Code
03080
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eue-Keun Choi, MD, PhD
Facility Name
Severance Cardiovascular Hospital
City
Seoul
ZIP/Postal Code
03722
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hui-Nam Pak, MD, PhD
Facility Name
Seoul Samsung Medical Center
City
Seoul
ZIP/Postal Code
06351
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Young Keun On, MD, PhD
Facility Name
Catholic University of Korea Yeouido St. Mary's Hospital
City
Seoul
ZIP/Postal Code
07345
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ju-Youn Kim, MD
Facility Name
Wonju Severance Christian Hospital
City
Wŏnju
ZIP/Postal Code
26426
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Min-Soo Ahn, MD, PhD

12. IPD Sharing Statement

Learn more about this trial

Resolution of Thrombi in Left Atrial Appendage With Edoxaban

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