<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/NCT02982850</url>
  </required_header>
  <id_info>
    <org_study_id>2016-0869</org_study_id>
    <nct_id>NCT02982850</nct_id>
  </id_info>
  <brief_title>Dabigatran Versus Conventional Treatment for Prevention of Silent Cerebral Infarct in Atrial Fibrillation Associated With Valvular Disease</brief_title>
  <acronym>DECISIVE</acronym>
  <official_title>Effectiveness of Dabigatran Versus Conventional Treatment for Prevention of Silent Cerebral Infarct in Aortic and Mitral Valvular Atrial Fibrillation Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Asan Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Boehringer Ingelheim</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Asan Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The prevalence of AF, which is tachyarrhythmia, is approximately 2% of the entire population&#xD;
      and 5% of the population at the age of 60 or older. AF is the cause of approximately 20% of&#xD;
      all events of ischemic stroke, and patients with AF are known to be at 6 to 10% risk of&#xD;
      ischemic stroke per year. Patients with valvular AF are known to have a higher incidence of&#xD;
      stroke than patients with nonvalvular AF. However, the relevant data are insufficient as&#xD;
      large randomized studies comparing NOAC treatment with warfarin, a conventional treatment,&#xD;
      did not include many patients with moderate and severe valvular AF.&#xD;
&#xD;
      Ischemic stroke is divided into symptomatic stroke with brain lesions on brain magnetic&#xD;
      resonance imaging (MRI) and silent cerebral infarct with lesions on brain MRI but without&#xD;
      stroke symptoms. According to a brain MRI follow-up study, the incidence of silent cerebral&#xD;
      infarct was 17.7% (254 subjects) over a period of 5 years, with 11.4% of 254 subjects&#xD;
      reporting to have experienced symptoms. This means that the incidence of silent cerebral&#xD;
      infarct is approximately 9 times that of symptomatic stroke. In addition, patients with a&#xD;
      history of silent cerebral infarct are known to be approximately twice more likely to&#xD;
      experience stroke in the future than those without a history of silent. Brain microbleed is&#xD;
      easily detected by brain MRI and is a well-known independent predictor of intraparenchymal&#xD;
      hemorrhage and silent cerebral infarct. The prevention of stroke by the study drug can be&#xD;
      indirectly assessed based on the incidence of silent cerebral infarct and brain microbleed on&#xD;
      brain MRI. Investigators tried to compare effect of dabigatran with conventional treatment in&#xD;
      terms of prevention of stroke by comparing incidences of silent cerebral infarct and brain&#xD;
      microbleed and symptomatic stroke using brain MRI.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Amongst different types of cardiac arrhythmia, tachyarrhythmia shows the highest prevalence.&#xD;
      The prevalence of AF, which is tachyarrhythmia, is approximately 2% of the entire population&#xD;
      and 5% of the population at the age of 60 or older. AF is the cause of approximately 20% of&#xD;
      all events of ischemic stroke, and patients with AF are known to be at 6 to 10% risk of&#xD;
      ischemic stroke per year. In addition, AF results in heart failure and doubles mortalities.&#xD;
      With an increase in the elderly population, there is a worldwide trend of increased&#xD;
      hospitalization rate and medical cost caused by cardiac arrhythmia. In addition, whereas AF&#xD;
      has been known to occur mainly in the elderly, the incidence of AF is also increasing in&#xD;
      younger population, which is thought to be associated with the increased prevalence of heart&#xD;
      diseases, dietary changes, and increased environmental pollution.&#xD;
&#xD;
      A. Previous studies related to atrial fibrillation and stroke i. While AF is characterized by&#xD;
      a single electrophysiological abnormality, depending on cases, the risk of stroke varies from&#xD;
      below 1%/year to 20%/year or above.&#xD;
&#xD;
      ii. New oral anticoagulant (NOAC), left atrial appendage occlusion, etc. have been studied as&#xD;
      treatments to replace warfarin and aspirin and their effects have been also demonstrated.&#xD;
&#xD;
      B. Relevant study trends and limitations i. Patients with valvular AF are known to have a&#xD;
      higher incidence of stroke than patients with nonvalvular AF. However, the relevant data are&#xD;
      insufficient as large randomized studies comparing NOAC treatment with warfarin, a&#xD;
      conventional treatment, did not include many patients with moderate and severe valvular AF.&#xD;
&#xD;
      ii. The exclusion of valvular AF from the study is based on the assumption that the&#xD;
      pathogenesis of thromboembolism would vary according to the type of AF. However, the&#xD;
      difference in pathogenesis of thromboembolism between valvular AF and nonvalvular AF remains&#xD;
      unknown.&#xD;
&#xD;
      C. Study features i. Ischemic stroke is divided into symptomatic stroke with brain lesions on&#xD;
      brain magnetic resonance imaging (MRI) and silent cerebral infarct with lesions on brain MRI&#xD;
      but without stroke symptoms.&#xD;
&#xD;
      ii. According to a brain MRI follow-up study, the incidence of silent cerebral infarct was&#xD;
      17.7% (254 subjects) over a period of 5 years, with 11.4% of 254 subjects reporting to have&#xD;
      experienced symptoms. This means that the incidence of silent cerebral infarct is&#xD;
      approximately 9 times that of symptomatic stroke.&#xD;
&#xD;
      iii. In addition, patients with a history of silent cerebral infarct are known to be&#xD;
      approximately twice more likely to experience stroke in the future than those without a&#xD;
      history of silent.&#xD;
&#xD;
      iv. Brain microbleed is easily detected by brain MRI and is a well-known independent&#xD;
      predictor of intraparenchymal hemorrhage and silent cerebral infarct.&#xD;
&#xD;
      v. The prevention of stroke by the study drug can be indirectly assessed based on the&#xD;
      incidence of silent cerebral infarct and brain microbleed on brain MRI at the start of study&#xD;
      and at 1 year follow-up.&#xD;
&#xD;
      D. Significance of the study i. The incidence of stroke is higher in valvular AF than in&#xD;
      nonvalvular AF. ii. There is lack of data on dabigatran treatment, an NOAC, in valvular AF.&#xD;
      iii. To compare dabigatran with conventional treatment in terms of prevention of stroke by&#xD;
      comparing incidences of silent cerebral infarct and brain microbleed and symptomatic stroke&#xD;
      at the start of study and at 1 year follow-up using brain MRI.&#xD;
&#xD;
      This is a single center, prospective, randomized study to evaluate the effectiveness and&#xD;
      safety of dabigatran versus conventional treatment in patients with valvular AF by comparing&#xD;
      the incidence of silent cerebral infarct and brain microbleed using brain MRI. Aspirin or&#xD;
      warfarin treatment will be continued in patients randomly allocated to conventional treatment&#xD;
      group, and changed to dabigatran treatment in those randomly allocated to dabigatran group.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>December 2016</start_date>
  <completion_date type="Actual">October 2020</completion_date>
  <primary_completion_date type="Actual">October 2020</primary_completion_date>
  <phase>Phase 4</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Composite of clinical cerebral infarct or new cerebral MRI lesions</measure>
    <time_frame>12 months</time_frame>
    <description>Number of patients who develop clinical symptomatic cerebral infarct or new cerebral MR lesion, including silent cerebral infarct and microbleed</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Silent cerebral infarct</measure>
    <time_frame>12 months</time_frame>
    <description>Asymptomatic cerebral infarct confirmed by MRI</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical cerebral infarct</measure>
    <time_frame>12 months</time_frame>
    <description>Symptomatic cerebral infarct</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>New cerebral microbleed</measure>
    <time_frame>12 months</time_frame>
    <description>Asymptomatic MRI lesion</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Major bleeding</measure>
    <time_frame>12 months</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">120</enrollment>
  <condition>Atrial Fibrillation</condition>
  <condition>Valve Heart Disease</condition>
  <arm_group>
    <arm_group_label>Dabigatran</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Previous treatment of aspirin or warfarin will be changed to dabigatran treatment in patients allocated to dabigatran group.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Conventional Treatment</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Acetylsalicylic acid or warfarin treatment will be continued in patients allocated to conventional treatment group.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dabigatran</intervention_name>
    <arm_group_label>Dabigatran</arm_group_label>
    <other_name>Pradaxa</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Acetylsalicylic acid</intervention_name>
    <arm_group_label>Conventional Treatment</arm_group_label>
    <other_name>Aspirin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Warfarin</intervention_name>
    <arm_group_label>Conventional Treatment</arm_group_label>
    <other_name>Coumadin</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Voluntary informed consent&#xD;
&#xD;
          -  Diagnosis of AF&#xD;
&#xD;
          -  Aortic valvular stenosis, aortic valvular regurgitation, mitral valvular stenosis, or&#xD;
             mitral valvular regurgitation of moderate or above severity&#xD;
&#xD;
          -  Patients must have one of the following:&#xD;
&#xD;
               -  Hypertension requiring medical treatment&#xD;
&#xD;
               -  Symptomatic heart failure, New York Heart Association class 2 or higher in the&#xD;
                  last 6 mon or ejection fraction &lt;40% documented by echocardiogram&#xD;
&#xD;
               -  Age ≥ 65 years&#xD;
&#xD;
               -  Diabetes mellitus on treatment&#xD;
&#xD;
               -  History of previous stroke, transient ischemic attack, or systemic embolism&#xD;
&#xD;
               -  Previous myocardial infarct, peripheral artery disease, or aortic plaque&#xD;
&#xD;
               -  Enlarged left atrial size ≥ 40mm documented by echocardiogram&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  An individual involved in planning or conducting this study&#xD;
&#xD;
          -  Unable to understand study conduct or study compliance due to dementia, etc.&#xD;
&#xD;
          -  Lack of ability to communicate&#xD;
&#xD;
          -  Pregnant woman&#xD;
&#xD;
          -  Past cardiac valve replacement&#xD;
&#xD;
          -  Stroke resulting in severe disabilities within the past 6 months&#xD;
&#xD;
          -  Stroke including silent cerebral infarct within the past 2 weeks&#xD;
&#xD;
          -  Chronic renal failure with creatinine clearance &lt; 30ml/min&#xD;
&#xD;
          -  Active hepatitis (≥2 fold increase in liver enzyme levels, known active hepatitis C,&#xD;
             active hepatitis B, active hepatitis A)&#xD;
&#xD;
          -  High bleeding risk&#xD;
&#xD;
               -  Major surgery within the past 1 month&#xD;
&#xD;
               -  Planned surgery or procedure within 3 months&#xD;
&#xD;
               -  Intracranial, intraocular, intraspinal, or retroperitoneal bleeding history or&#xD;
                  atraumatic joint bleeding history&#xD;
&#xD;
               -  Digestive tract bleeding within the past 1 year&#xD;
&#xD;
               -  Symptomatic or endoscopically confirmed gastric or duodenal ulcer within the past&#xD;
                  30 days&#xD;
&#xD;
               -  Hematologic abnormalities&#xD;
&#xD;
               -  Requiring anticoagulant treatment for any reasons other than AF&#xD;
&#xD;
               -  Requiring antithrombotics within 48 hours of start of the study&#xD;
&#xD;
               -  Uncontrolled hypertension (systolic blood pressure ≥180mmHg or diastolic blood&#xD;
                  pressure ≥100mmHg)&#xD;
&#xD;
               -  Recent malignant tumor or 6 months or longer treatment with radiation therapy&#xD;
&#xD;
               -  Mean life expectancy ≤3 years&#xD;
&#xD;
          -  Contraindication of anticoagulant treatment&#xD;
&#xD;
          -  Screening test results as follows&#xD;
&#xD;
               -  Platelet count &lt;80,000 cells/mm3&#xD;
&#xD;
               -  Hemoglobin level &lt;10g/dL&#xD;
&#xD;
          -  Previous experience of major bleeding complications&#xD;
&#xD;
          -  Participation in another drug study within 3 months prior to enrollment to this study&#xD;
&#xD;
          -  Administration of the study drug within 1 month prior to enrollment to this study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>19 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Duk-Hyun Kang, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Asan Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Asan Medical Center</name>
      <address>
        <city>Seoul</city>
        <zip>138-736</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <verification_date>January 2021</verification_date>
  <study_first_submitted>November 29, 2016</study_first_submitted>
  <study_first_submitted_qc>December 5, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 6, 2016</study_first_posted>
  <last_update_submitted>January 11, 2021</last_update_submitted>
  <last_update_submitted_qc>January 11, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">January 13, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Asan Medical Center</investigator_affiliation>
    <investigator_full_name>Duk-Hyun Kang</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Atrial Fibrillation</keyword>
  <keyword>Valvular Insufficiency</keyword>
  <keyword>Valvular Stenosis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cerebral Infarction</mesh_term>
    <mesh_term>Atrial Fibrillation</mesh_term>
    <mesh_term>Heart Diseases</mesh_term>
    <mesh_term>Heart Valve Diseases</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Aspirin</mesh_term>
    <mesh_term>Warfarin</mesh_term>
    <mesh_term>Dabigatran</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/NCT02982850
org study id: 2016-0869
nct id: NCT02982850
lead sponsor: 
collaborator: 
has dmc: Yes
The prevalence of AF, which is tachyarrhythmia, is approximately 2% of the entire population
      and 5% of the population at the age of 60 or older. AF is the cause of approximately 20% of
      all events of ischemic stroke, and patients with AF are known to be at 6 to 10% risk of
      ischemic stroke per year. Patients with valvular AF are known to have a higher incidence of
      stroke than patients with nonvalvular AF. However, the relevant data are insufficient as
      large randomized studies comparing NOAC treatment with warfarin, a conventional treatment,
      did not include many patients with moderate and severe valvular AF.

      Ischemic stroke is divided into symptomatic stroke with brain lesions on brain magnetic
      resonance imaging (MRI) and silent cerebral infarct with lesions on brain MRI but without
      stroke symptoms. According to a brain MRI follow-up study, the incidence of silent cerebral
      infarct was 17.7% (254 subjects) over a period of 5 years, with 11.4% of 254 subjects
      reporting to have experienced symptoms. This means that the incidence of silent cerebral
      infarct is approximately 9 times that of symptomatic stroke. In addition, patients with a
      history of silent cerebral infarct are known to be approximately twice more likely to
      experience stroke in the future than those without a history of silent. Brain microbleed is
      easily detected by brain MRI and is a well-known independent predictor of intraparenchymal
      hemorrhage and silent cerebral infarct. The prevention of stroke by the study drug can be
      indirectly assessed based on the incidence of silent cerebral infarct and brain microbleed on
      brain MRI. Investigators tried to compare effect of dabigatran with conventional treatment in
      terms of prevention of stroke by comparing incidences of silent cerebral infarct and brain
      microbleed and symptomatic stroke using brain MRI.
Amongst different types of cardiac arrhythmia, tachyarrhythmia shows the highest prevalence.
      The prevalence of AF, which is tachyarrhythmia, is approximately 2% of the entire population
      and 5% of the population at the age of 60 or older. AF is the cause of approximately 20% of
      all events of ischemic stroke, and patients with AF are known to be at 6 to 10% risk of
      ischemic stroke per year. In addition, AF results in heart failure and doubles mortalities.
      With an increase in the elderly population, there is a worldwide trend of increased
      hospitalization rate and medical cost caused by cardiac arrhythmia. In addition, whereas AF
      has been known to occur mainly in the elderly, the incidence of AF is also increasing in
      younger population, which is thought to be associated with the increased prevalence of heart
      diseases, dietary changes, and increased environmental pollution.

      A. Previous studies related to atrial fibrillation and stroke i. While AF is characterized by
      a single electrophysiological abnormality, depending on cases, the risk of stroke varies from
      below 1%/year to 20%/year or above.

      ii. New oral anticoagulant (NOAC), left atrial appendage occlusion, etc. have been studied as
      treatments to replace warfarin and aspirin and their effects have been also demonstrated.

      B. Relevant study trends and limitations i. Patients with valvular AF are known to have a
      higher incidence of stroke than patients with nonvalvular AF. However, the relevant data are
      insufficient as large randomized studies comparing NOAC treatment with warfarin, a
      conventional treatment, did not include many patients with moderate and severe valvular AF.

      ii. The exclusion of valvular AF from the study is based on the assumption that the
      pathogenesis of thromboembolism would vary according to the type of AF. However, the
      difference in pathogenesis of thromboembolism between valvular AF and nonvalvular AF remains
      unknown.

      C. Study features i. Ischemic stroke is divided into symptomatic stroke with brain lesions on
      brain magnetic resonance imaging (MRI) and silent cerebral infarct with lesions on brain MRI
      but without stroke symptoms.

      ii. According to a brain MRI follow-up study, the incidence of silent cerebral infarct was
      17.7% (254 subjects) over a period of 5 years, with 11.4% of 254 subjects reporting to have
      experienced symptoms. This means that the incidence of silent cerebral infarct is
      approximately 9 times that of symptomatic stroke.

      iii. In addition, patients with a history of silent cerebral infarct are known to be
      approximately twice more likely to experience stroke in the future than those without a
      history of silent.

      iv. Brain microbleed is easily detected by brain MRI and is a well-known independent
      predictor of intraparenchymal hemorrhage and silent cerebral infarct.

      v. The prevention of stroke by the study drug can be indirectly assessed based on the
      incidence of silent cerebral infarct and brain microbleed on brain MRI at the start of study
      and at 1 year follow-up.

      D. Significance of the study i. The incidence of stroke is higher in valvular AF than in
      nonvalvular AF. ii. There is lack of data on dabigatran treatment, an NOAC, in valvular AF.
      iii. To compare dabigatran with conventional treatment in terms of prevention of stroke by
      comparing incidences of silent cerebral infarct and brain microbleed and symptomatic stroke
      at the start of study and at 1 year follow-up using brain MRI.

      This is a single center, prospective, randomized study to evaluate the effectiveness and
      safety of dabigatran versus conventional treatment in patients with valvular AF by comparing
      the incidence of silent cerebral infarct and brain microbleed using brain MRI. Aspirin or
      warfarin treatment will be continued in patients randomly allocated to conventional treatment
      group, and changed to dabigatran treatment in those randomly allocated to dabigatran group.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Composite of clinical cerebral infarct or new cerebral MRI lesions
time frame: 12 months
description: Number of patients who develop clinical symptomatic cerebral infarct or new cerebral MR lesion, including silent cerebral infarct and microbleed
measure: Silent cerebral infarct
time frame: 12 months
description: Asymptomatic cerebral infarct confirmed by MRI
measure: Clinical cerebral infarct
time frame: 12 months
description: Symptomatic cerebral infarct
measure: New cerebral microbleed
time frame: 12 months
description: Asymptomatic MRI lesion
measure: Major bleeding
time frame: 12 months
arm group label: Dabigatran
arm group type: Experimental
description: Previous treatment of aspirin or warfarin will be changed to dabigatran treatment in patients allocated to dabigatran group.
arm group label: Conventional Treatment
arm group type: Active Comparator
description: Acetylsalicylic acid or warfarin treatment will be continued in patients allocated to conventional treatment group.
intervention type: Drug
intervention name: Dabigatran
arm group label: Dabigatran
other name: Pradaxa
intervention type: Drug
intervention name: Acetylsalicylic acid
arm group label: Conventional Treatment
other name: Aspirin
intervention type: Drug
intervention name: Warfarin
arm group label: Conventional Treatment
other name: Coumadin
criteria: 
gender: All
minimum age: 19 Years
maximum age: N/A
healthy volunteers: No
last name: Duk-Hyun Kang, M.D.
role: Principal Investigator
affiliation: Asan Medical Center
facility: 
country: Korea, Republic of
responsible party type: Principal Investigator
investigator affiliation: Asan Medical Center
investigator full name: Duk-Hyun Kang
investigator title: Professor
mesh term: Cerebral Infarction
mesh term: Atrial Fibrillation
mesh term: Heart Diseases
mesh term: Heart Valve Diseases
mesh term: Aspirin
mesh term: Warfarin
mesh term: Dabigatran
sharing ipd: No