<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03840291</url>
  </required_header>
  <id_info>
    <org_study_id>2018-09-041</org_study_id>
    <nct_id>NCT03840291</nct_id>
  </id_info>
  <brief_title>Resolution of Thrombi in Left Atrial Appendage With Edoxaban</brief_title>
  <acronym>REFLEX</acronym>
  <official_title>Resolution of Thrombi in Left Atrial Appendage With Edoxaban</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Keimyung University Dongsan Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Daiichi Sankyo Korea Co., Ltd., a Daiichi Sankyo Company</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Keimyung University Dongsan Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Non-valvular (NV) atrial fibrillation (AF) increases the risk of stroke by approximately&#xD;
      fivefold. The atrial thrombi associated with AF are seen within the left atrial appendage&#xD;
      (LAA) in most cases (&gt; 90%). Anticoagulation with a vitamin-K antagonist (VKA) is recommended&#xD;
      to prevent thromboembolic complications and to resolve thrombi. Non-VKA oral anticoagulants&#xD;
      (NOACs) have replaced the VKA for the thromboprophylaxis in patients with NVAF since 2010.&#xD;
      Therefore, NOAC can be the excellent alternative to VKA concerning resolving preexisting LAA&#xD;
      thrombi because of its rapid onset of action and no need of bridging with heparin. However,&#xD;
      there is still lack of data regarding the optimal treatment for patients with AF and thrombi&#xD;
      in LAA with NOAC. There are only several case reports of the efficacy of NOACs in resolving&#xD;
      LAA thrombi available.&#xD;
&#xD;
      Edoxaban, which has data showing efficacy and safety in thromboprophylaxis, can be the new&#xD;
      option for treatment of patients with AF and LAA thrombi. The purpose of this study is to&#xD;
      evaluate the efficacy of Edoxaban in resolving the LAA thrombi, which is related with&#xD;
      nonvalvular AF.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">May 19, 2019</start_date>
  <completion_date type="Anticipated">August 2024</completion_date>
  <primary_completion_date type="Anticipated">October 2023</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>complete resolution of LAA thrombi</measure>
    <time_frame>6 weeks</time_frame>
    <description>The percentage of subjects with complete resolution of LAA thrombi</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Treatment responses of thrombi</measure>
    <time_frame>6 weeks</time_frame>
    <description>Treatment responses of thrombi: Number of participants with resolved, reduced, unchanged, enlarged thrombi or newly appeared thrombi</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ischemic stroke event</measure>
    <time_frame>12 weeks</time_frame>
    <description>The percentage of subjects who experienced ischemic stroke</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Bleeding event</measure>
    <time_frame>12 weeks</time_frame>
    <description>The percentage of subjects who experienced bleeding event</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Atrial Fibrillation</condition>
  <condition>Left Atrial Appendage Thrombosis</condition>
  <arm_group>
    <arm_group_label>Edoxaban treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <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.&#xD;
Patients in this group are taking Lixiana® (Edoxaban) 60mg for resolution of left atrial appendage thrombi&#xD;
Reduced (30mg) dose is administered in patients with one or more of the following clinical factors:&#xD;
Moderate or severe renal impairment (creatinine clearance (CrCL) 15 - 50 mL/min)&#xD;
Low body weight ≤ 60 kg&#xD;
Concomitant use of the following P-glycoprotein (P-gp) inhibitors: ciclosporin,dronedarone, erythromycin, or ketoconazole.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Edoxaban</intervention_name>
    <description>Edoxaban will be used for resolution of left atrial appendage thrombi</description>
    <arm_group_label>Edoxaban treatment</arm_group_label>
    <other_name>Lixiana®</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Men or women aged ≥ 20 years&#xD;
&#xD;
          -  Hemodynamically stable nonvalvular AF or atrial flutter&#xD;
&#xD;
          -  LAA thrombus documented by TEE up to 72 hours prior to start of study medication&#xD;
&#xD;
          -  VKA or NOAC-naïve or untreated within 1 month prior to sign the informed consent&#xD;
&#xD;
          -  VKA pretreated but under the therapeutic International Normalized ratio levels (&lt;2.0;&#xD;
             documented with at least 2 consecutive measurements that are at least 24 hours apart)&#xD;
             within last 6 weeks&#xD;
&#xD;
          -  Women of childbearing potential and men must agree to use adequate contraception when&#xD;
             sexually active&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Transient Ischemic Attack within 3 days prior to study inclusion&#xD;
&#xD;
          -  Severe, disabling stroke (modified Rankin score of 4-5, inclusive) within 3 months or&#xD;
             any stroke within 14 days before the start of study drug&#xD;
&#xD;
          -  Acute thromboembolic events or thrombosis (venous/arterial) within the last 14 days&#xD;
             prior to study inclusion&#xD;
&#xD;
          -  Acute myocardial infarction within the last 14 days prior to study inclusion&#xD;
&#xD;
          -  Cardiac-related criteria: Previous intracardiac thrombus, Free-floating ball thrombus,&#xD;
             Intracardiac tumor, known left ventricular or aortic thrombus&#xD;
&#xD;
          -  Active bleeding or high risk for bleeding contraindicating anticoagulant therapy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Seongwook Han, M.D., Ph.D.</last_name>
    <role>Study Chair</role>
    <affiliation>Keimyung University Dongsan Medical Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jongmin Hwang, M.D., Ph.D.</last_name>
    <phone>+82-53-250-7333</phone>
    <email>dsmcep@dsmc.or.kr</email>
  </overall_contact>
  <location>
    <facility>
      <name>Keimyung University Dongsan Medical Center</name>
      <address>
        <city>Daegu</city>
        <zip>41931</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jongmin Hwang, M.D.</last_name>
      <phone>+82-53-250-7333</phone>
      <email>dsmcep@dsmc.or.kr</email>
    </contact>
    <investigator>
      <last_name>Seongwook Han, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Hyoung-Seob Park, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Jongmin Hwang, MD, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Division of Cardiology, Department of Internal Medicine, Kyungpook National University Hospital</name>
      <address>
        <city>Daegu</city>
        <zip>41944</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Myung Hwan Bae, MD, PhD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Division of Cardiology, Department of Internal Medicine, Yeungnam University Hospital</name>
      <address>
        <city>Daegu</city>
        <zip>42415</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Dong Gu Shin, MD, PhD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Division of Cardiology, Department of Internal Medicine, Daegu Catholic University Medical Center</name>
      <address>
        <city>Daegu</city>
        <zip>42472</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Young Soo Lee, MD, PhD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Catholic University of Korea, Incheon St. Mary's hospital</name>
      <address>
        <city>Incheon</city>
        <zip>21431</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Yoori Kim, MD, PhD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Pusan National University Hospital</name>
      <address>
        <city>Pusan</city>
        <zip>49241</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jinhee Ahn, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Korea University Anam Hospital</name>
      <address>
        <city>Seoul</city>
        <zip>02841</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jong-Il Choi, MD, PhD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Seoul National University Hospital</name>
      <address>
        <city>Seoul</city>
        <zip>03080</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Eue-Keun Choi, MD, PhD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Severance Cardiovascular Hospital</name>
      <address>
        <city>Seoul</city>
        <zip>03722</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Hui-Nam Pak, MD, PhD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Seoul Samsung Medical Center</name>
      <address>
        <city>Seoul</city>
        <zip>06351</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Young Keun On, MD, PhD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Catholic University of Korea Yeouido St. Mary's Hospital</name>
      <address>
        <city>Seoul</city>
        <zip>07345</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ju-Youn Kim, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Wonju Severance Christian Hospital</name>
      <address>
        <city>Wŏnju</city>
        <zip>26426</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Min-Soo Ahn, MD, PhD</last_name>
    </contact>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>February 11, 2019</study_first_submitted>
  <study_first_submitted_qc>February 11, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 15, 2019</study_first_posted>
  <last_update_submitted>May 27, 2023</last_update_submitted>
  <last_update_submitted_qc>May 27, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 31, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Keimyung University Dongsan Medical Center</investigator_affiliation>
    <investigator_full_name>Seongwook Han</investigator_full_name>
    <investigator_title>Professor of Internal Medicine</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Atrial Fibrillation</mesh_term>
    <mesh_term>Thrombosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Edoxaban</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03840291
org study id: 2018-09-041
nct id: NCT03840291
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
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.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: complete resolution of LAA thrombi
time frame: 6 weeks
description: The percentage of subjects with complete resolution of LAA thrombi
measure: Treatment responses of thrombi
time frame: 6 weeks
description: Treatment responses of thrombi: Number of participants with resolved, reduced, unchanged, enlarged thrombi or newly appeared thrombi
measure: Ischemic stroke event
time frame: 12 weeks
description: The percentage of subjects who experienced ischemic stroke
measure: Bleeding event
time frame: 12 weeks
description: The percentage of subjects who experienced bleeding event
arm group label: Edoxaban treatment
arm group type: Experimental
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: Edoxaban
description: Edoxaban will be used for resolution of left atrial appendage thrombi
arm group label: Edoxaban treatment
other name: Lixiana®
criteria: 
gender: All
minimum age: 20 Years
maximum age: N/A
healthy volunteers: No
last name: Seongwook Han, M.D., Ph.D.
role: Study Chair
affiliation: Keimyung University Dongsan Medical Center
last name: Jongmin Hwang, M.D., Ph.D.
phone: +82-53-250-7333
email: dsmcep@dsmc.or.kr
facility: 
status: Recruiting
contact: 
investigator: 
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
contact: 
country: Korea, Republic of
responsible party type: Principal Investigator
investigator affiliation: Keimyung University Dongsan Medical Center
investigator full name: Seongwook Han
investigator title: Professor of Internal Medicine
mesh term: Atrial Fibrillation
mesh term: Thrombosis
mesh term: Edoxaban