Atrial FibrillationPhase 4REFLEXNCT03840291
Resolution of Thrombi in Left Atrial Appendage With Edoxaban
A Phase 4 study testing Edoxaban in people with Atrial Fibrillation and Left Atrial Appendage Thrombosis, run by Keimyung University Dongsan Medical Center at 12 sites in South Korea.
Trial 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%). Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Atrial Fibrillation, Left Atrial Appendage Thrombosis
- What is being tested?
- Edoxaban
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 12 sitesSouth Korea
- Study dates
- 19 May 2019to 1 Aug 2024
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
South Korea12 sites
Keimyung University Dongsan Medical Center
Daegu, 41931
Division of Cardiology, Department of Internal Medicine, Kyungpook National University Hospital
Daegu, 41944
Division of Cardiology, Department of Internal Medicine, Yeungnam University Hospital
Daegu, 42415
Division of Cardiology, Department of Internal Medicine, Daegu Catholic University Medical Center
Daegu, 42472
Catholic University of Korea, Incheon St. Mary's hospital
Incheon, 21431
Pusan National University Hospital
Pusan, 49241
Korea University Anam Hospital
Seoul, 02841
Seoul National University Hospital
Seoul, 03080
Severance Cardiovascular Hospital
Seoul, 03722
Seoul Samsung Medical Center
Seoul, 06351
Catholic University of Korea Yeouido St. Mary's Hospital
Seoul, 07345
Wonju Severance Christian Hospital
Wŏnju, 26426
About this study
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.
- Being tested
- Edoxaban
- Medical subject headings
- Atrial Fibrillation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EdoxabanDrug
Also called Lixiana®
Edoxaban will be used for resolution of left atrial appendage thrombi
| Study group | Role | What they receive |
|---|---|---|
| Edoxaban treatment | Experimental | 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. Receives: Drug: Edoxaban |
What is being measured
The primary outcome is the main question the study is designed to answer.
complete resolution of LAA thrombi
The percentage of subjects with complete resolution of LAA thrombi
Measured: 6 weeks
Secondary outcomes (3)
Treatment responses of thrombi
Treatment responses of thrombi: Number of participants with resolved, reduced, unchanged, enlarged thrombi or newly appeared thrombi
Measured: 6 weeks
Ischemic stroke event
The percentage of subjects who experienced ischemic stroke
Measured: 12 weeks
Bleeding event
The percentage of subjects who experienced bleeding event
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Feb 2019
- Study start19 May 2019
- Primary completion30 Oct 2023
- Study completion1 Aug 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Atrial FibrillationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- Keimyung University Dongsan Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Daiichi Sankyo Korea Co., Ltd., a Daiichi Sankyo Company
- Responsible party
- Principal investigator, Seongwook Han, Keimyung University Dongsan Medical Center
- Investigators
- Seongwook Han, M.D., Ph.D., Study chair, Keimyung University Dongsan Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03840291
- Sponsor's protocol ID
- 2018-09-041
- Acronym
- REFLEX
- Status last verified
- Aug 2024
- First submitted
- 11 Feb 2019
- Last updated
- 19 Aug 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Resolution of Thrombi in Left Atrial Appendage With Edoxaban
- ClinicalTrials.gov ID
- NCT03840291
- Acronym / sponsor ID
- REFLEX / 2018-09-041
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- Keimyung University Dongsan Medical CenterUniversity, hospital or other
- Collaborators
- Daiichi Sankyo Korea Co., Ltd., a Daiichi Sankyo Company
- Study start
- 19 May 2019 (actual)
- Primary completion
- 30 Oct 2023 (actual)
- Study completion
- 1 Aug 2024 (actual)
- First posted
- 15 Feb 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Edoxaban treatment | Experimental | Drug: Edoxaban1. 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. |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EdoxabanAlso: Lixiana®Edoxaban will be used for resolution of left atrial appendage thrombi | Drug | Edoxaban treatment |
Primary outcome
complete resolution of LAA thrombi
Time frame: 6 weeks
The percentage of subjects with complete resolution of LAA thrombi
3 secondary outcomes
Treatment responses of thrombi
Time frame: 6 weeks
Ischemic stroke event
Time frame: 12 weeks
Bleeding event
Time frame: 12 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Aug 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Seongwook Han, M.D., Ph.D. study chair
Keimyung University Dongsan Medical Center
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Edoxaban in people with Atrial Fibrillation and Left Atrial Appendage Thrombosis, run by Keimyung University Dongsan Medical Center at 12 sites in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
complete resolution of LAA thrombi (time frame: 6 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Aug 2024.