<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/NCT02985268</url>
  </required_header>
  <id_info>
    <org_study_id>MHICC-2016-001</org_study_id>
    <nct_id>NCT02985268</nct_id>
  </id_info>
  <brief_title>Evaluation of Outcomes of CRT and MitraClip for Treatment of Low Ejection Fraction and Functional Mitral Regurgitation in HF</brief_title>
  <acronym>EVOLVE-HF</acronym>
  <official_title>Evaluation of Outcomes of Cardiac Resynchronization Therapy and MitraClip for the Treatment of Low Ejection Fraction and Functional Mitral Valve Regurgitation in Heart Failure</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Montreal Heart Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Montreal Heart Institute</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      At present, the optimal treatment strategy for heart failure patients and moderate-to-severe&#xD;
      (3+) or severe (4+) mitral regurgitation with a class IIa recommendation for CRT is&#xD;
      uncertain.Whether these patents should also be treated for functional mitral regurgitation or&#xD;
      with CRT also remains unclear. We therefore propose a randomized 2x2 factorial design in this&#xD;
      patient population to understand the the impact of both CRT and transcatheter mitral valve&#xD;
      repair with the MitraClip on their functional status and quality of life.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Withdrawn</overall_status>
  <start_date>December 2016</start_date>
  <completion_date type="Anticipated">February 2020</completion_date>
  <primary_completion_date type="Anticipated">December 2019</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>Factorial Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Improvement in distance walked on a six-minute walk test (6MWT)</measure>
    <time_frame>Baseline to 6 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in cardiographic endpoints</measure>
    <time_frame>Baseline to 6 months</time_frame>
    <description>Mitral regurgitation severity</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in cardiographic endpoints</measure>
    <time_frame>Baseline to 6 months</time_frame>
    <description>Indexed left ventricular end-systolic volume (LVESVi)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in cardiographic endpoints</measure>
    <time_frame>Baseline to 6 months</time_frame>
    <description>Left ventricular ejection fraction (LVEF)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Quality of Life Assessment scores</measure>
    <time_frame>Baseline to 6 months</time_frame>
    <description>Kansas City Cardiomyopathy Questionnaire (KCCQ)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Quality of Life Assessment scores</measure>
    <time_frame>Baseline to 6 months</time_frame>
    <description>Euro Quality of Life Questionnaire (EQ5DL)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Re-hospitalizations for decompensated heart failure</measure>
    <time_frame>6 and 12 months</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Wearable activity/heart rate sensor (Fitbit Charge 2)</measure>
    <time_frame>12 months</time_frame>
    <description>Assessments obtained from the wearable activity/heart rate sensor:&#xD;
Mean daily heart rate&#xD;
Daily heart rate range calculated as the difference between min and max heart rate&#xD;
number of daily steps&#xD;
number of daily hours of sleep</description>
  </other_outcome>
  <other_outcome>
    <measure>Major Adverse Cardiac Event (MACE)</measure>
    <time_frame>12 months</time_frame>
    <description>Time to major adverse cardiac events:&#xD;
Cardiovascular death&#xD;
All -cause mortality&#xD;
non-fatal Myocardial Infarction&#xD;
fatal and non-fatal stroke&#xD;
rehospitalization for decompensated heart failure</description>
  </other_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Functional Mitral Regurgitation</condition>
  <condition>Heart Failure</condition>
  <arm_group>
    <arm_group_label>MitraClip/Optimal Medical Therapy (OMT) and CRT ON</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patient to be implanted with both MitraClip and CRT-D. Will also receive optimal medical therapy. CRT-D will be programmed to ON</description>
  </arm_group>
  <arm_group>
    <arm_group_label>MitraClip/OMT and CRT OFF</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patient to be implanted with both MitraClip and CRT-D. Will also receive optimal medical therapy. CRT-D will be programmed to OFF until the 6-month follow-up visit in which the CRT will be turned ON</description>
  </arm_group>
  <arm_group>
    <arm_group_label>OMT and CRT ON</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patient to be implanted with only the CRT-D and will receive optimal medical therapy.&#xD;
CRT-D will be programmed to ON</description>
  </arm_group>
  <arm_group>
    <arm_group_label>OMT and CRT OFF</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patient to be implanted with only the CRT-D and will receive optimal medical therapy.&#xD;
CRT-D will be programmed to OFF until the 6-month follow-up visit in which the CRT will be turned ON</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>MitraClip</intervention_name>
    <description>The MitraClip Clip Delivery System is indicated for the percutaneous reduction of significant symptomatic mitral regurgitation (MR ≥ 3+) due to primary abnormality of the mitral apparatus [degenerative MR] in patients who have been determined to be at prohibitive risk for mitral valve surgery by a heart team, which includes a cardiac surgeon experienced in mitral valve surgery and a cardiologist experienced in mitral valve disease, and in whom existing comorbidities would not preclude the expected benefit from reduction of the mitral regurgitation.</description>
    <arm_group_label>MitraClip/OMT and CRT OFF</arm_group_label>
    <arm_group_label>MitraClip/Optimal Medical Therapy (OMT) and CRT ON</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Optimal Medical Therapy</intervention_name>
    <description>Optimal medical therapy administered as per the Guideline Direct Medical Therapy (GDMT) as defined in the 2013 ACCF/AHA Heart Failure Guidelines with maximum tolerated doses of an ACE-inhibitor or Angiotensin Receptor Blocker (ARB) and beta-blocker</description>
    <arm_group_label>MitraClip/OMT and CRT OFF</arm_group_label>
    <arm_group_label>MitraClip/Optimal Medical Therapy (OMT) and CRT ON</arm_group_label>
    <arm_group_label>OMT and CRT OFF</arm_group_label>
    <arm_group_label>OMT and CRT ON</arm_group_label>
    <other_name>OMT</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>CRT-D</intervention_name>
    <description>Cardiac Resynchronization Therapy with defibrillation therapy devices will be implanted according to the Heart Rhythm Society Guidelines for implanted devices.</description>
    <arm_group_label>MitraClip/OMT and CRT OFF</arm_group_label>
    <arm_group_label>MitraClip/Optimal Medical Therapy (OMT) and CRT ON</arm_group_label>
    <arm_group_label>OMT and CRT OFF</arm_group_label>
    <arm_group_label>OMT and CRT ON</arm_group_label>
    <other_name>Cardiac Resynchronization Therapy and Defibrillator</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Symptomatic moderate-to-severe (3+) or severe (4+) functional mitral regurgitation due&#xD;
             to cardiomyopathy of either ischemic or non-ischemic etiology as determined by&#xD;
             transthoracic echocardiogram (TTE), and confirmed by the Echocardiography Core Lab&#xD;
             (ECL);&#xD;
&#xD;
          2. Symptomatic heart failure as defined by New York Heart Association (NYHA) class II,&#xD;
             III or ambulatory IV;&#xD;
&#xD;
          3. Treatment and compliance with optimal medical therapy for heart failure for at least&#xD;
             30 days; Optimal medical therapy is defined by: Maximum tolerated beta-blocker,&#xD;
             angiotensin converting enzyme inhibitor (ACE) or angiotensin receptor blocker (ARB),&#xD;
             and aldosterone antagonist (as per the ACCF/AHA Guidelines as judged by the HF&#xD;
             specialist investigator on site and confirmed by the Clinical Eligibility Committee).&#xD;
&#xD;
          4. Left ventricular ejection fraction ≤ 35%, as assessed by any one of the following&#xD;
             methods: echocardiography, contrast left ventriculography, gated blood pool scan or&#xD;
             cardiac magnetic resonance imaging (MRI);&#xD;
&#xD;
          5. Class IIa indication for cardiac resynchronization therapy:&#xD;
&#xD;
               1. Left bundle branch block (LBBB) and QRS duration of 120-149 ms;&#xD;
&#xD;
               2. Right bundle branch block (RBBB) and QRS ≥ 150 ms.&#xD;
&#xD;
          6. Clinical agreement amongst local investigators that the patient will not be offered&#xD;
             surgical intervention;&#xD;
&#xD;
          7. The primary regurgitant jet, in the opinion of the MitraClip implanting investigator,&#xD;
             can successfully be treated by the MitraClip. Treatment of commissural mitral&#xD;
             regurgitation may be treated at the discretion of the operator. All major jets&#xD;
             contributing the secondary MR will be treated with the MitraClip;&#xD;
&#xD;
          8. Ability to perform a six-minute walk test (6MWT) without substantial physical&#xD;
             limitations and without use of a walker or wheelchair and distance walked in 6 minutes&#xD;
             of ≤ 450m;&#xD;
&#xD;
          9. Ability and willingness to give written informed consent and to comply with the&#xD;
             requirements of the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Life expectancy less than 12 months due to noncardiac conditions;&#xD;
&#xD;
          2. ACC/AHA Stage D Heart Failure;&#xD;
&#xD;
          3. Left ventricular ejection fraction ≤ 15%;&#xD;
&#xD;
          4. Hypotension (systolic pressure &lt;90 mm Hg) or requirement for inotropic support or&#xD;
             mechanical hemodynamic support;&#xD;
&#xD;
          5. United Network for Organ Sharing (UNOS) status 1 heart transplantation or prior&#xD;
             orthotopic heart transplantation;&#xD;
&#xD;
          6. Untreated clinically significant coronary artery disease requiring revascularization;&#xD;
&#xD;
          7. CABG within prior 30 days;&#xD;
&#xD;
          8. Percutaneous coronary intervention within prior 30 days;&#xD;
&#xD;
          9. Severe Chronic Obstructive Pulmonary Disease (COPD) requiring continuous daytime home&#xD;
             oxygen or chronic oral corticosteroid therapy;&#xD;
&#xD;
         10. Previous surgical mitral valve bioprosthesis, mitral annuloplasty, or transcatheter&#xD;
             mitral valve procedure;&#xD;
&#xD;
         11. Positive pregnancy test, or woman of child bearing potential not using highly&#xD;
             effective methods of contraception;&#xD;
&#xD;
         12. Mitral valve area &lt;4.0 cm2 as assessed by planimetry of the mitral valve;&#xD;
&#xD;
         13. Subjects in whom trans-esophageal echocardiography is contraindicated or high risk;&#xD;
&#xD;
         14. Mitral leaflet anatomy which may preclude MitraClip implantation:&#xD;
&#xD;
               1. Perforated mitral leaflets or clefts, lack of primary or secondary chordal&#xD;
                  support;&#xD;
&#xD;
               2. Severe calcification in the grasping area;&#xD;
&#xD;
               3. Rheumatic valve disease.&#xD;
&#xD;
         15. Previously implanted Cardiac Resynchronization Therapy and Defibrillator (CRT-D)&#xD;
             system;&#xD;
&#xD;
         16. Stroke or transient ischemic event within 30 days before randomization;&#xD;
&#xD;
         17. Modified Rankin Scale &gt;4 disability;&#xD;
&#xD;
         18. Need for emergent or urgent surgery for any reason or any planned cardiac surgery&#xD;
             within the next 12 months;&#xD;
&#xD;
         19. Severe renal impairment defined as an Estimated Glomerular Filtration Rate (eGFR) &lt;30&#xD;
             mL/min/1.73m2 as calculated by the Modification in Diet in Renal Disease (MDRD)&#xD;
             formula;&#xD;
&#xD;
         20. Severe anemia requiring transfusional support or therapy with erythropoietin;&#xD;
&#xD;
         21. Physical evidence of right-sided congestive heart failure with echocardiographic&#xD;
             evidence of moderate or severe right ventricular dysfunction;&#xD;
&#xD;
         22. Aortic valve disease requiring surgery or transcatheter intervention;&#xD;
&#xD;
         23. Significant tricuspid valve disease requiring surgical intervention or very severe&#xD;
             tricuspid regurgitation;&#xD;
&#xD;
         24. Active infection requiring antibiotic therapy;&#xD;
&#xD;
         25. Active endocarditis or active rheumatic heart disease or leaflets degenerated from&#xD;
             rheumatic disease;&#xD;
&#xD;
         26. Echocardiographic evidence of intracardiac mass, thrombus or vegetation;&#xD;
&#xD;
         27. Any condition making it unlikely the patient will be able to complete all protocol&#xD;
             procedures (including compliance with guideline directed medical therapy) and&#xD;
             follow-up visits;&#xD;
&#xD;
         28. Presence of any of the following:&#xD;
&#xD;
               1. Pulmonary artery systolic pressure (PASP) &gt; 70 mm Hg confirmed by right heart&#xD;
                  catheterization;&#xD;
&#xD;
               2. Infiltrative cardiomyopathies.&#xD;
&#xD;
         29. Any other condition(s) that would compromise the safety of the patient as judged by&#xD;
             the site principal investigator.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Anita Asgar, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Montreal Heart Institute</affiliation>
  </overall_official>
  <verification_date>February 2020</verification_date>
  <study_first_submitted>December 1, 2016</study_first_submitted>
  <study_first_submitted_qc>December 2, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 7, 2016</study_first_posted>
  <last_update_submitted>February 26, 2020</last_update_submitted>
  <last_update_submitted_qc>February 26, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">February 27, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>MitraClip</keyword>
  <keyword>Cardiovascular resynchronization therapy</keyword>
  <keyword>Six minute walk test</keyword>
  <keyword>Mitral regurgitation</keyword>
  <keyword>CRT-D</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Heart Failure</mesh_term>
    <mesh_term>Mitral Valve Insufficiency</mesh_term>
  </condition_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/NCT02985268
org study id: MHICC-2016-001
nct id: NCT02985268
lead sponsor: 
has dmc: Yes
At present, the optimal treatment strategy for heart failure patients and moderate-to-severe
      (3+) or severe (4+) mitral regurgitation with a class IIa recommendation for CRT is
      uncertain.Whether these patents should also be treated for functional mitral regurgitation or
      with CRT also remains unclear. We therefore propose a randomized 2x2 factorial design in this
      patient population to understand the the impact of both CRT and transcatheter mitral valve
      repair with the MitraClip on their functional status and quality of life.
allocation: Randomized
intervention model: Factorial Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Outcomes Assessor)
measure: Improvement in distance walked on a six-minute walk test (6MWT)
time frame: Baseline to 6 months
measure: Change in cardiographic endpoints
time frame: Baseline to 6 months
description: Mitral regurgitation severity
measure: Change in cardiographic endpoints
time frame: Baseline to 6 months
description: Indexed left ventricular end-systolic volume (LVESVi)
measure: Change in cardiographic endpoints
time frame: Baseline to 6 months
description: Left ventricular ejection fraction (LVEF)
measure: Change in Quality of Life Assessment scores
time frame: Baseline to 6 months
description: Kansas City Cardiomyopathy Questionnaire (KCCQ)
measure: Change in Quality of Life Assessment scores
time frame: Baseline to 6 months
description: Euro Quality of Life Questionnaire (EQ5DL)
measure: Number of Re-hospitalizations for decompensated heart failure
time frame: 6 and 12 months
measure: Wearable activity/heart rate sensor (Fitbit Charge 2)
time frame: 12 months
description: Assessments obtained from the wearable activity/heart rate sensor:
Mean daily heart rate
Daily heart rate range calculated as the difference between min and max heart rate
number of daily steps
number of daily hours of sleep
measure: Major Adverse Cardiac Event (MACE)
time frame: 12 months
description: Time to major adverse cardiac events:
Cardiovascular death
All -cause mortality
non-fatal Myocardial Infarction
fatal and non-fatal stroke
rehospitalization for decompensated heart failure
arm group label: MitraClip/Optimal Medical Therapy (OMT) and CRT ON
arm group type: Active Comparator
description: Patient to be implanted with both MitraClip and CRT-D. Will also receive optimal medical therapy. CRT-D will be programmed to ON
arm group label: MitraClip/OMT and CRT OFF
arm group type: Active Comparator
description: Patient to be implanted with both MitraClip and CRT-D. Will also receive optimal medical therapy. CRT-D will be programmed to OFF until the 6-month follow-up visit in which the CRT will be turned ON
arm group label: OMT and CRT ON
arm group type: Active Comparator
description: Patient to be implanted with only the CRT-D and will receive optimal medical therapy.
CRT-D will be programmed to ON
arm group label: OMT and CRT OFF
arm group type: Active Comparator
description: Patient to be implanted with only the CRT-D and will receive optimal medical therapy.
CRT-D will be programmed to OFF until the 6-month follow-up visit in which the CRT will be turned ON
intervention type: Device
intervention name: MitraClip
description: The MitraClip Clip Delivery System is indicated for the percutaneous reduction of significant symptomatic mitral regurgitation (MR ≥ 3+) due to primary abnormality of the mitral apparatus [degenerative MR] in patients who have been determined to be at prohibitive risk for mitral valve surgery by a heart team, which includes a cardiac surgeon experienced in mitral valve surgery and a cardiologist experienced in mitral valve disease, and in whom existing comorbidities would not preclude the expected benefit from reduction of the mitral regurgitation.
arm group label: MitraClip/OMT and CRT OFF
arm group label: MitraClip/Optimal Medical Therapy (OMT) and CRT ON
intervention type: Drug
intervention name: Optimal Medical Therapy
description: Optimal medical therapy administered as per the Guideline Direct Medical Therapy (GDMT) as defined in the 2013 ACCF/AHA Heart Failure Guidelines with maximum tolerated doses of an ACE-inhibitor or Angiotensin Receptor Blocker (ARB) and beta-blocker
arm group label: MitraClip/OMT and CRT OFF
arm group label: MitraClip/Optimal Medical Therapy (OMT) and CRT ON
arm group label: OMT and CRT OFF
arm group label: OMT and CRT ON
other name: OMT
intervention type: Device
intervention name: CRT-D
description: Cardiac Resynchronization Therapy with defibrillation therapy devices will be implanted according to the Heart Rhythm Society Guidelines for implanted devices.
arm group label: MitraClip/OMT and CRT OFF
arm group label: MitraClip/Optimal Medical Therapy (OMT) and CRT ON
arm group label: OMT and CRT OFF
arm group label: OMT and CRT ON
other name: Cardiac Resynchronization Therapy and Defibrillator
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Anita Asgar, MD
role: Principal Investigator
affiliation: Montreal Heart Institute
responsible party type: Sponsor
mesh term: Heart Failure
mesh term: Mitral Valve Insufficiency
sharing ipd: No