<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/NCT03792152</url>
  </required_header>
  <id_info>
    <org_study_id>REVIEW-AF</org_study_id>
    <nct_id>NCT03792152</nct_id>
  </id_info>
  <brief_title>A Trial of Rivaroxaban Versus Warfarin in Dissolving Left Atrial Appendage Thrombus in Patients With Atrial Fibrillation</brief_title>
  <official_title>A Prospective Randomized Controlled Trial of Rivaroxaban Versus Warfarin in Dissolving Left Atrial Appendage Thrombus in Patients With Atrial Fibrillation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The Second Affiliated Hospital of Chongqing Medical University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>The Second Affiliated Hospital of Chongqing Medical University</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>
      The purpose of this clinical randomized trial is to evaluate the efficacy and safety of&#xD;
      rivaroxaban compared with warfarin in dissolving the LAA thrombus in patients with atrial&#xD;
      fibrillation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Left atrial appendage (LAA) thrombosis is a common complication of atrial fibrillation and&#xD;
      will significantly increase the incidence of stroke in patients. Warfarin is a classical oral&#xD;
      anticoagulant which can dissolve thrombus, but its clinical use has many limitations and it&#xD;
      requires strict monitoring of coagulation. Recently, some studies have shown that NOAC&#xD;
      (dabigatran / rivaroxaban) can dissolve left atrial appendage thrombosis. The application of&#xD;
      rivaroxaban in the X-TRA study dissolved 41.5% of LAA thrombus after 6 weeks, indicating its&#xD;
      potential clinical application prospects. Whether rivaroxaban is not inferior to warfarin for&#xD;
      rapid dissolution of LAA thrombus, there is no prospective randomized controlled trial.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">June 1, 2019</start_date>
  <completion_date type="Anticipated">December 30, 2022</completion_date>
  <primary_completion_date type="Anticipated">January 1, 2022</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>two groups, group one is for Rivaroxaban 20mg qd (15mg qd If creatinine clearance is between 30-49ml/min), group two is for warfarin, keep the INR between 2-3.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>After receiving the informed consent form patient, The heads of the centers randomly extracted the envelopes and patients are included in the study based on random envelope grouping results.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Number of patient who's thrombus in the left atrium or left atrial appendage is completely dissolved within 3 to 6 weeks</measure>
    <time_frame>6 weeks</time_frame>
    <description>Transesophageal echocardiography was used to assess whether there was a left atrial appendage thrombus at 3rd, 6th week after initiation of anticoagulant therapy.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of patient who's thrombus in the left atrium or left atrial appendage is completely dissolved within 12 weeks</measure>
    <time_frame>12 weeks</time_frame>
    <description>Transesophageal echocardiography was used to assess whether there was a left atrial appendage thrombus at 12th week after initiation of anticoagulant therapy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Size change of left atrial appendage or left atrium thrombus</measure>
    <time_frame>12 weeks</time_frame>
    <description>If a left atrial appendage or left atrial thrombus is detected,then the size of the thrombus is measured using echocardiography。</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of severe bleeding cases such as gastrointestinal bleeding and cerebral hemorrhage.</measure>
    <time_frame>12 weeks</time_frame>
    <description>Number of severe bleeding cases such as gastrointestinal bleeding and cerebral hemorrhage.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of transient ischemic attacks (TIA) and strokes</measure>
    <time_frame>12 weeks</time_frame>
    <description>Number of transient ischemic attacks (TIA) and strokes</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">80</enrollment>
  <condition>Atrial Fibrillation</condition>
  <condition>Left Atrial Appendage Thrombosis</condition>
  <condition>Rivaroxaban</condition>
  <arm_group>
    <arm_group_label>rivaroxaban</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>After diagnosis of left atrial appendage thrombus by transesophageal echocardiography, then start with rivaroxaba 20mg qd(15mg If creatinine clearance is between 30-49 ml/min ).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Warfarin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>After diagnosis of left atrial appendage thrombus by transesophageal echocardiography, subcutaneous injection of low molecular weight heparin and oral warfarin treatment were started, and low molecular weight heparin was stopped after INR reached 2.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rivaroxaban</intervention_name>
    <description>After diagnosis of left atrial appendage thrombus by transesophageal echocardiography, then start with rivaroxaba 20mg qd (15mg If creatinine clearance is between 30-49 ml/min).</description>
    <arm_group_label>rivaroxaban</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Warfarin</intervention_name>
    <description>After the diagnosis of left atrial appendage thrombus by transesophageal echocardiography, subcutaneous injection of low molecular weight heparin (4000iu q12h) and oral warfarin treatment were started, and low molecular weight heparin was stopped after INR reached 2.</description>
    <arm_group_label>Warfarin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Get informed consent from the patient or family.&#xD;
&#xD;
          2. Non-valvular atrial fibrillation / atrial flutter.&#xD;
&#xD;
          3. The first transesophageal echocardiogram revealed a left atrial appendage thrombus&#xD;
             (within 7 days of detection of thrombus).&#xD;
&#xD;
          4. Age at 18-80 years old.&#xD;
&#xD;
          5. CrCL≥ 30 mL/min (Cockcroft-Gault).&#xD;
&#xD;
          6. AST/ALT is less than 2 times the upper limit of normal.&#xD;
&#xD;
          7. Women of childbearing age need contraception.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Pregnant or lactating woman.&#xD;
&#xD;
          2. Can't understand or follow the research plan.&#xD;
&#xD;
          3. Patients under 18 or over 80 years old.&#xD;
&#xD;
          4. Low weight (&lt; 40 kg).&#xD;
&#xD;
          5. Previously found LAA thrombus and have taken anticoagulant drugs.&#xD;
&#xD;
          6. Patients with contraindications for anticoagulation.&#xD;
&#xD;
          7. Patients who need to use antiplatelet drugs simultaneously within 6-12 months after&#xD;
             ACS or PCI.&#xD;
&#xD;
          8. A history of cerebral hemorrhage.&#xD;
&#xD;
          9. Patients with active bleeding.&#xD;
&#xD;
         10. Severe gastritis, gastroesophageal reflux patients.&#xD;
&#xD;
         11. Combination of P-glycoprotein inhibitors and other drugs in the presence of NOAC&#xD;
             contraindications.&#xD;
&#xD;
        13.Patient with tumor. 14.Planned surgery within 3 months. 15.Other investigators believe&#xD;
        that patients are not suitable for enrollment.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>ZHIYU LING, MD</last_name>
    <phone>+8613512362075</phone>
    <email>lingzy1977@163.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>YANPING XU</last_name>
    <phone>+86-023-63693079</phone>
  </overall_contact_backup>
  <results_reference>
    <citation>Lip GY, Hammerstingl C, Marin F, Cappato R, Meng IL, Kirsch B, van Eickels M, Cohen A; X-TRA study and CLOT-AF registry investigators. Left atrial thrombus resolution in atrial fibrillation or flutter: Results of a prospective study with rivaroxaban (X-TRA) and a retrospective observational registry providing baseline data (CLOT-AF). Am Heart J. 2016 Aug;178:126-34. doi: 10.1016/j.ahj.2016.05.007. Epub 2016 May 17.</citation>
    <PMID>27502860</PMID>
  </results_reference>
  <verification_date>March 2019</verification_date>
  <study_first_submitted>December 31, 2018</study_first_submitted>
  <study_first_submitted_qc>December 31, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">January 3, 2019</study_first_posted>
  <last_update_submitted>March 18, 2019</last_update_submitted>
  <last_update_submitted_qc>March 18, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">March 19, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>The Second Affiliated Hospital of Chongqing Medical University</investigator_affiliation>
    <investigator_full_name>Yuehui Yin</investigator_full_name>
    <investigator_title>professor</investigator_title>
  </responsible_party>
  <keyword>Atrial Fibrillation</keyword>
  <keyword>Left Atrial Appendage Thrombosis</keyword>
  <keyword>rivaroxaban</keyword>
  <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>Warfarin</mesh_term>
    <mesh_term>Rivaroxaban</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03792152
org study id: REVIEW-AF
nct id: NCT03792152
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The purpose of this clinical randomized trial is to evaluate the efficacy and safety of
      rivaroxaban compared with warfarin in dissolving the LAA thrombus in patients with atrial
      fibrillation.
Left atrial appendage (LAA) thrombosis is a common complication of atrial fibrillation and
      will significantly increase the incidence of stroke in patients. Warfarin is a classical oral
      anticoagulant which can dissolve thrombus, but its clinical use has many limitations and it
      requires strict monitoring of coagulation. Recently, some studies have shown that NOAC
      (dabigatran / rivaroxaban) can dissolve left atrial appendage thrombosis. The application of
      rivaroxaban in the X-TRA study dissolved 41.5% of LAA thrombus after 6 weeks, indicating its
      potential clinical application prospects. Whether rivaroxaban is not inferior to warfarin for
      rapid dissolution of LAA thrombus, there is no prospective randomized controlled trial.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: two groups, group one is for Rivaroxaban 20mg qd (15mg qd If creatinine clearance is between 30-49ml/min), group two is for warfarin, keep the INR between 2-3.
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: After receiving the informed consent form patient, The heads of the centers randomly extracted the envelopes and patients are included in the study based on random envelope grouping results.
measure: Number of patient who's thrombus in the left atrium or left atrial appendage is completely dissolved within 3 to 6 weeks
time frame: 6 weeks
description: Transesophageal echocardiography was used to assess whether there was a left atrial appendage thrombus at 3rd, 6th week after initiation of anticoagulant therapy.
measure: Number of patient who's thrombus in the left atrium or left atrial appendage is completely dissolved within 12 weeks
time frame: 12 weeks
description: Transesophageal echocardiography was used to assess whether there was a left atrial appendage thrombus at 12th week after initiation of anticoagulant therapy.
measure: Size change of left atrial appendage or left atrium thrombus
time frame: 12 weeks
description: If a left atrial appendage or left atrial thrombus is detected,then the size of the thrombus is measured using echocardiography。
measure: Number of severe bleeding cases such as gastrointestinal bleeding and cerebral hemorrhage.
time frame: 12 weeks
description: Number of severe bleeding cases such as gastrointestinal bleeding and cerebral hemorrhage.
measure: Number of transient ischemic attacks (TIA) and strokes
time frame: 12 weeks
description: Number of transient ischemic attacks (TIA) and strokes
arm group label: rivaroxaban
arm group type: Experimental
description: After diagnosis of left atrial appendage thrombus by transesophageal echocardiography, then start with rivaroxaba 20mg qd(15mg If creatinine clearance is between 30-49 ml/min ).
arm group label: Warfarin
arm group type: Active Comparator
description: After diagnosis of left atrial appendage thrombus by transesophageal echocardiography, subcutaneous injection of low molecular weight heparin and oral warfarin treatment were started, and low molecular weight heparin was stopped after INR reached 2.
intervention type: Drug
intervention name: Rivaroxaban
description: After diagnosis of left atrial appendage thrombus by transesophageal echocardiography, then start with rivaroxaba 20mg qd (15mg If creatinine clearance is between 30-49 ml/min).
arm group label: rivaroxaban
intervention type: Drug
intervention name: Warfarin
description: After the diagnosis of left atrial appendage thrombus by transesophageal echocardiography, subcutaneous injection of low molecular weight heparin (4000iu q12h) and oral warfarin treatment were started, and low molecular weight heparin was stopped after INR reached 2.
arm group label: Warfarin
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: ZHIYU LING, MD
phone: +8613512362075
email: lingzy1977@163.com
last name: YANPING XU
phone: +86-023-63693079
citation: Lip GY, Hammerstingl C, Marin F, Cappato R, Meng IL, Kirsch B, van Eickels M, Cohen A; X-TRA study and CLOT-AF registry investigators. Left atrial thrombus resolution in atrial fibrillation or flutter: Results of a prospective study with rivaroxaban (X-TRA) and a retrospective observational registry providing baseline data (CLOT-AF). Am Heart J. 2016 Aug;178:126-34. doi: 10.1016/j.ahj.2016.05.007. Epub 2016 May 17.
PMID: 27502860
responsible party type: Principal Investigator
investigator affiliation: The Second Affiliated Hospital of Chongqing Medical University
investigator full name: Yuehui Yin
investigator title: professor
mesh term: Atrial Fibrillation
mesh term: Thrombosis
mesh term: Warfarin
mesh term: Rivaroxaban
sharing ipd: No