<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/NCT01703806</url>
  </required_header>
  <id_info>
    <org_study_id>2007-0264</org_study_id>
    <nct_id>NCT01703806</nct_id>
  </id_info>
  <brief_title>Early Surgery Versus Conventional Treatment for Asymptomatic Severe Mitral Regurgitation</brief_title>
  <official_title>Early Surgery Versus Conventional Treatment for Asymptomatic Patients With Severe Degenerative Mitral Regurgitation: A Propensity Analysis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Asan Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Asan Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The timing of surgical intervention in asymptomatic patients with severe degenerative mitral&#xD;
      regurgitation (MR) remains controversial. The benefit of early surgery has been suggested in&#xD;
      prospective, observational studies, whereas a watchful waiting strategy seemed to be safe and&#xD;
      effective in the other prospective study. The consensus guidelines for the performance of&#xD;
      early surgery in asymptomatic patients with severe MR are different, reflecting controversy.&#xD;
      Clinical outcome in asymptomatic patients with MR is poorly defined and it is important to&#xD;
      identify high-risk patients in whom early surgery may be warranted. Thus, the investigators&#xD;
      try to compare long-term outcomes of early surgery with those of a conventional-treatment&#xD;
      strategy in a large prospective cohort of asymptomatic patients with severe degenerative MR&#xD;
      using a propensity analysis, and to identify high-risk subgroups to whom early surgery is&#xD;
      more beneficial.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Surgery is the only definitive therapy for severe mitral regurgitation (MR) and the&#xD;
      guidelines recommend surgery for management of MR to symptomatic patients or asymptomatic&#xD;
      patients with left ventricular (LV) dysfunction. However, the timing of surgical intervention&#xD;
      in asymptomatic patients with severe MR remains unclear due to the lack of randomized&#xD;
      clinical trials comparing early surgery versus watchful waiting. The benefit of early surgery&#xD;
      has been suggested in prospective, observational studies, whereas a watchful waiting strategy&#xD;
      seemed to be safe and effective in the other prospective study. The consensus guidelines for&#xD;
      the performance of early surgery in asymptomatic patients with severe MR are different,&#xD;
      reflecting controversy. The 2006 American College of Cardiology/American Heart Association&#xD;
      (ACC/AHA) guidelines recommend early surgery for asymptomatic patients if the success rate of&#xD;
      mitral valve repair is expected to exceed 90%, but the 2007 European Society of Cardiology&#xD;
      (ESC) guidelines recommend watchful waiting for such patients.&#xD;
&#xD;
      Clinical outcome in asymptomatic patients with MR is poorly defined and it is important to&#xD;
      identify high-risk patients in whom early surgery may be warranted. Older patients and those&#xD;
      with a larger effective regurgitant orifice (ERO) showed increased mortality under medical&#xD;
      management, but it is controversial whether early surgery would improve clinical outcome of&#xD;
      such patients, because the performance of surgery in high-risk patients might be associated&#xD;
      with increased operative risk. Although randomized trials are required to establish&#xD;
      indications for early surgery, ethical and financial constraints do not allow us to conduct a&#xD;
      randomized trial and the investigators choose to perform a propensity analysis in a large&#xD;
      prospective cohort of patients. The investigators try to compare long-term outcomes of early&#xD;
      surgery with those of a conventional-treatment strategy that is based on current guidelines&#xD;
      in a large prospective cohort of asymptomatic patients with severe degenerative MR using a&#xD;
      propensity analysis, and examine the hypothesis that the reduction in cardiac mortality or&#xD;
      cardiac event by early surgery is particularly evident among patients aged &gt; 50 years or&#xD;
      those with ERO ≥ 0.4 square centimeter.&#xD;
&#xD;
      All patients suspected of MR undergo transthoracic echocardiography. Entry evaluation&#xD;
      includes demographic data, clinical presentation, physical findings and echocardiographic&#xD;
      data. Eligibility is determined after a patient undergoes a thorough evaluation of clinical&#xD;
      and echocardiographic data. After the eligible patient has signed informed consent, entry&#xD;
      into the registry will take place. The treatment groups will not be randomly assigned and the&#xD;
      choice of early surgery or conventional treatment for each patient is at the discretion of&#xD;
      the attending physician, who explains the potential benefits of early surgery and procedural&#xD;
      risks in detail and considers the preferences of individual patients most importantly.&#xD;
      Patients in the early surgery group should undergo mitral valve surgery within 6 months of&#xD;
      enrollment. Patients in the conventional treatment group will be treated according to the&#xD;
      2006 ACC/AHA guidelines and they will be educated to report immediately to a study&#xD;
      coordinator or an investigator if they experience any symptoms, and referred for surgery if&#xD;
      exertional dyspnea, LV ejection fraction &lt;0.60, LV end-systolic dimension &gt;40 mm, Doppler&#xD;
      estimated pulmonary artery pressure &gt; 50 mmHg, or atrial fibrillation develops. All patients&#xD;
      will be followed at 3 months, 6 months, and 1 year; and at 6-month intervals thereafter until&#xD;
      close-out of the study, and educated to call a study coordinator or an investigator if they&#xD;
      experience any adverse events.&#xD;
&#xD;
      The Executive Committee will approve the final trial design and protocol. This committee will&#xD;
      also be responsible for reviewing the final results, determining the methods of presentation&#xD;
      and publication, and selection of secondary projects and publications. Members of the&#xD;
      committee will include the PI and persons who will organize this study. The Data Safety&#xD;
      Monitoring Board (DSMB) will review the safety data from this study and make recommendations&#xD;
      based on safety analyses of serious adverse events and protocol deviation. The Clinical&#xD;
      Events Committee will meet regularly to review and adjudicate all clinical events that occur&#xD;
      throughout the study period. The statistical analysis will be performed according to the&#xD;
      prespecified analysis plan as described in the study protocol.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">December 2007</start_date>
  <completion_date type="Anticipated">August 2023</completion_date>
  <primary_completion_date type="Anticipated">August 2023</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Cardiac mortality</measure>
    <time_frame>Up to 10 years</time_frame>
    <description>Cardiac mortality is defined as operative mortality, sudden cardiac death, death from complications of myocardial infarction, heart failure, complications of cardiac intervention or other cardiac disease. Operative mortality is defined as death within 30 days of mitral valve surgery.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Repeat mitral valve surgery</measure>
    <time_frame>Up to 10 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hospitalization due to congestive heart failure</measure>
    <time_frame>Up to 10 years</time_frame>
    <description>A congestive heart failure hospitalization is defined as an unplanned, urgent admission for the management of congestive heart failure . A patient admitted for congestive heart failure have to show resting dyspnea and radiological signs of pulmonary edema and require intravenous diuretics.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>A composite of cardiac events</measure>
    <time_frame>Up to 10 years</time_frame>
    <description>A composite of cardiac mortality, repeat MV surgery and hospitalization due to congestive heart failure during follow-up.</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">600</enrollment>
  <condition>Mitral Regurgitation</condition>
  <arm_group>
    <arm_group_label>Conventional Treatment</arm_group_label>
    <description>Patients in the conventional treatment group will be treated according to the 2006 ACC/AHA guidelines and they will be referred for surgery if they experience any symptoms, and referred for surgery if exertional dyspnea, LV ejection fraction &lt;0.60, LV end-systolic dimension &gt;40 mm, Doppler estimated pulmonary artery pressure &gt; 50 mmHg, or atrial fibrillation develops.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Early Surgery</arm_group_label>
    <description>Patients in the early surgery group should undergo mitral valve surgery within 6 months of enrollment.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Early Surgery</intervention_name>
    <description>MItral valve surgery</description>
    <arm_group_label>Early Surgery</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Watchful Observation</intervention_name>
    <description>Watchful observation</description>
    <arm_group_label>Conventional Treatment</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        From 2007 to 2016, 600 consecutive, asymptomatic patients with severe degenerative MR who&#xD;
        are potential candidates for early surgery, will be enrolled in the present study. Severe&#xD;
        degenerative MR is defined as severe prolapse and/or flail leaflet of the mitral valve with&#xD;
        a proximal isovelocity surface area (PISA) radius &gt; 8 mm.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  asymptomatic patients&#xD;
&#xD;
          -  severe degenerative MR&#xD;
&#xD;
          -  preserved left ventricular systolic function&#xD;
&#xD;
        Exclusion Criteria: According to the recommendations of the 2006 American College of&#xD;
        Cardiology/American Heart Association (ACC/AHA) guidelines for surgical indications of&#xD;
        severe MR, the criteria for exclusion from the study are defined as follows.&#xD;
&#xD;
          -  patients with the presence of exertional dyspnea, or angina&#xD;
&#xD;
          -  left ventricular ejection fraction &lt; 0.60&#xD;
&#xD;
          -  left ventricular end-systolic dimension &gt; 40 mm&#xD;
&#xD;
          -  atrial fibrillation&#xD;
&#xD;
          -  significant aortic valve disease&#xD;
&#xD;
          -  Doppler-estimated systolic pulmonary artery pressure &gt; 50 mmHg&#xD;
&#xD;
          -  patients who were not candidates for early surgery based on age &gt; 80 years and&#xD;
             coexisting malignancies&#xD;
&#xD;
          -  patients who did not consent to participate&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Duk-Hyun Kang, MD, PhD</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>
  <reference>
    <citation>Kang DH, Kim JH, Rim JH, Kim MJ, Yun SC, Song JM, Song H, Choi KJ, Song JK, Lee JW. Comparison of early surgery versus conventional treatment in asymptomatic severe mitral regurgitation. Circulation. 2009 Feb 17;119(6):797-804. doi: 10.1161/CIRCULATIONAHA.108.802314. Epub 2009 Feb 2.</citation>
    <PMID>19188506</PMID>
  </reference>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>October 8, 2012</study_first_submitted>
  <study_first_submitted_qc>October 10, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 11, 2012</study_first_posted>
  <last_update_submitted>February 6, 2023</last_update_submitted>
  <last_update_submitted_qc>February 6, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 8, 2023</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>Mitral regurgitation</keyword>
  <keyword>Mitral valve repair</keyword>
  <keyword>Watchful waiting</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mitral Valve Insufficiency</mesh_term>
  </condition_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/NCT01703806
org study id: 2007-0264
nct id: NCT01703806
lead sponsor: 
has dmc: Yes
The timing of surgical intervention in asymptomatic patients with severe degenerative mitral
      regurgitation (MR) remains controversial. The benefit of early surgery has been suggested in
      prospective, observational studies, whereas a watchful waiting strategy seemed to be safe and
      effective in the other prospective study. The consensus guidelines for the performance of
      early surgery in asymptomatic patients with severe MR are different, reflecting controversy.
      Clinical outcome in asymptomatic patients with MR is poorly defined and it is important to
      identify high-risk patients in whom early surgery may be warranted. Thus, the investigators
      try to compare long-term outcomes of early surgery with those of a conventional-treatment
      strategy in a large prospective cohort of asymptomatic patients with severe degenerative MR
      using a propensity analysis, and to identify high-risk subgroups to whom early surgery is
      more beneficial.
Surgery is the only definitive therapy for severe mitral regurgitation (MR) and the
      guidelines recommend surgery for management of MR to symptomatic patients or asymptomatic
      patients with left ventricular (LV) dysfunction. However, the timing of surgical intervention
      in asymptomatic patients with severe MR remains unclear due to the lack of randomized
      clinical trials comparing early surgery versus watchful waiting. The benefit of early surgery
      has been suggested in prospective, observational studies, whereas a watchful waiting strategy
      seemed to be safe and effective in the other prospective study. The consensus guidelines for
      the performance of early surgery in asymptomatic patients with severe MR are different,
      reflecting controversy. The 2006 American College of Cardiology/American Heart Association
      (ACC/AHA) guidelines recommend early surgery for asymptomatic patients if the success rate of
      mitral valve repair is expected to exceed 90%, but the 2007 European Society of Cardiology
      (ESC) guidelines recommend watchful waiting for such patients.

      Clinical outcome in asymptomatic patients with MR is poorly defined and it is important to
      identify high-risk patients in whom early surgery may be warranted. Older patients and those
      with a larger effective regurgitant orifice (ERO) showed increased mortality under medical
      management, but it is controversial whether early surgery would improve clinical outcome of
      such patients, because the performance of surgery in high-risk patients might be associated
      with increased operative risk. Although randomized trials are required to establish
      indications for early surgery, ethical and financial constraints do not allow us to conduct a
      randomized trial and the investigators choose to perform a propensity analysis in a large
      prospective cohort of patients. The investigators try to compare long-term outcomes of early
      surgery with those of a conventional-treatment strategy that is based on current guidelines
      in a large prospective cohort of asymptomatic patients with severe degenerative MR using a
      propensity analysis, and examine the hypothesis that the reduction in cardiac mortality or
      cardiac event by early surgery is particularly evident among patients aged > 50 years or
      those with ERO ≥ 0.4 square centimeter.

      All patients suspected of MR undergo transthoracic echocardiography. Entry evaluation
      includes demographic data, clinical presentation, physical findings and echocardiographic
      data. Eligibility is determined after a patient undergoes a thorough evaluation of clinical
      and echocardiographic data. After the eligible patient has signed informed consent, entry
      into the registry will take place. The treatment groups will not be randomly assigned and the
      choice of early surgery or conventional treatment for each patient is at the discretion of
      the attending physician, who explains the potential benefits of early surgery and procedural
      risks in detail and considers the preferences of individual patients most importantly.
      Patients in the early surgery group should undergo mitral valve surgery within 6 months of
      enrollment. Patients in the conventional treatment group will be treated according to the
      2006 ACC/AHA guidelines and they will be educated to report immediately to a study
      coordinator or an investigator if they experience any symptoms, and referred for surgery if
      exertional dyspnea, LV ejection fraction <0.60, LV end-systolic dimension >40 mm, Doppler
      estimated pulmonary artery pressure > 50 mmHg, or atrial fibrillation develops. All patients
      will be followed at 3 months, 6 months, and 1 year; and at 6-month intervals thereafter until
      close-out of the study, and educated to call a study coordinator or an investigator if they
      experience any adverse events.

      The Executive Committee will approve the final trial design and protocol. This committee will
      also be responsible for reviewing the final results, determining the methods of presentation
      and publication, and selection of secondary projects and publications. Members of the
      committee will include the PI and persons who will organize this study. The Data Safety
      Monitoring Board (DSMB) will review the safety data from this study and make recommendations
      based on safety analyses of serious adverse events and protocol deviation. The Clinical
      Events Committee will meet regularly to review and adjudicate all clinical events that occur
      throughout the study period. The statistical analysis will be performed according to the
      prespecified analysis plan as described in the study protocol.
observational model: Cohort
time perspective: Prospective
measure: Cardiac mortality
time frame: Up to 10 years
description: Cardiac mortality is defined as operative mortality, sudden cardiac death, death from complications of myocardial infarction, heart failure, complications of cardiac intervention or other cardiac disease. Operative mortality is defined as death within 30 days of mitral valve surgery.
measure: Repeat mitral valve surgery
time frame: Up to 10 years
measure: Hospitalization due to congestive heart failure
time frame: Up to 10 years
description: A congestive heart failure hospitalization is defined as an unplanned, urgent admission for the management of congestive heart failure . A patient admitted for congestive heart failure have to show resting dyspnea and radiological signs of pulmonary edema and require intravenous diuretics.
measure: A composite of cardiac events
time frame: Up to 10 years
description: A composite of cardiac mortality, repeat MV surgery and hospitalization due to congestive heart failure during follow-up.
arm group label: Conventional Treatment
description: Patients in the conventional treatment group will be treated according to the 2006 ACC/AHA guidelines and they will be referred for surgery if they experience any symptoms, and referred for surgery if exertional dyspnea, LV ejection fraction <0.60, LV end-systolic dimension >40 mm, Doppler estimated pulmonary artery pressure > 50 mmHg, or atrial fibrillation develops.
arm group label: Early Surgery
description: Patients in the early surgery group should undergo mitral valve surgery within 6 months of enrollment.
intervention type: Procedure
intervention name: Early Surgery
description: MItral valve surgery
arm group label: Early Surgery
intervention type: Procedure
intervention name: Watchful Observation
description: Watchful observation
arm group label: Conventional Treatment
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 20 Years
maximum age: 80 Years
healthy volunteers: No
last name: Duk-Hyun Kang, MD, PhD
role: Principal Investigator
affiliation: Asan Medical Center
facility: 
country: Korea, Republic of
citation: Kang DH, Kim JH, Rim JH, Kim MJ, Yun SC, Song JM, Song H, Choi KJ, Song JK, Lee JW. Comparison of early surgery versus conventional treatment in asymptomatic severe mitral regurgitation. Circulation. 2009 Feb 17;119(6):797-804. doi: 10.1161/CIRCULATIONAHA.108.802314. Epub 2009 Feb 2.
PMID: 19188506
responsible party type: Principal Investigator
investigator affiliation: Asan Medical Center
investigator full name: Duk-Hyun Kang
investigator title: Professor
mesh term: Mitral Valve Insufficiency