xml: <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/NCT05965258</url>
    </required_header>
    <id_info>
      <org_study_id>23-702</org_study_id>
      <secondary_id>1R01HL170090-01</secondary_id>
      <nct_id>NCT05965258</nct_id>
    </id_info>
    <brief_title>Phenotypic Classification of FMR With CMR</brief_title>
    <official_title>Improving Phenotypic Classification and Prediction of Treatment Outcomes in Patients With Non-ischemic Cardiomyopathy and Functional Mitral Regurgitation</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>The Cleveland Clinic</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>National Heart, Lung, and Blood Institute (NHLBI)</agency>
        <agency_class>NIH</agency_class>
      </collaborator>
    </sponsors>
    <source>The Cleveland Clinic</source>
    <oversight_info>
      <has_dmc>No</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 goal of the current research is to develop personalized risk prediction for functional&#xD;
        mitral regurgitation (FMR) patients through explainable unsupervised phenomapping enriched&#xD;
        with advanced cardiac magnetic resonance (CMR) imaging biomarkers, and to determine the CMR&#xD;
        predictors of reverse remodeling following modern therapies for FMR.&#xD;
  &#xD;
        The prospective study entails aiming to recruit 360 adult patients (ages &gt;18 years) with EF&#xD;
        10-50% and FMR RF&gt; 20%, who are clinically referred for CMR evaluation. Patients who enroll&#xD;
        in our study will be referred for optimization of mGDMT and will undergo follow-up CMR&#xD;
        studies at 6months. NICM patients who are fully medically optimized with significant FMR at&#xD;
        the time of the baseline CMR and are referred for Mitraclip treatment will undergo follow-up&#xD;
        CMR 6 months from Mitraclip intervention. NICM patients referred for mGDMT optimization, but&#xD;
        have persistent or progressive FMR at the time of 6 month follow-up CMR and referred for&#xD;
        Mitraclip therapy, will undergo a 2nd follow-up CMR 6 months from Mitraclip therapy.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Functional mitral regurgitation (FMR) portends a bleak prognosis and is a common consequence&#xD;
        of ischemic and non-ischemic cardiomyopathy (ICM, NICM), where adverse annular and left&#xD;
        ventricular (LV) remodeling and/or infarction alters mitral valve (MV) function.&#xD;
  &#xD;
        Prior studies demonstrate significant increases in mortality risk as severity of FMR&#xD;
        increases; mortality rates range from 15-40% at 1 year. Furthermore, as the prevalence of&#xD;
        heart failure (HF) is rising, FMR is projected to double from over 2 million patients in 2000&#xD;
        to over 4 million patients in the United States by 2030. Defining FMR severity, optimal&#xD;
        timing of intervention, and most appropriate method for intervention remain controversial.&#xD;
        Recently, MITRA-FR and COAPT trials demonstrated contrasting survival benefit with&#xD;
        percutaneous MV repair, demonstrating the importance and need for more optimal selection&#xD;
        criteria. Currently, the patient selection criteria for Mitraclip therapy are solely based on&#xD;
        MV anatomy and controversial echocardiographic criteria for FMR severity. Cardiac magnetic&#xD;
        resonance (CMR) provides an exciting opportunity to address numerous unmet needs regarding&#xD;
        characterizing FMR and the need for more optimal selection criteria for improving outcomes.&#xD;
        Superior accuracy and reproducibility for quantification of LV size and function, and gold&#xD;
        standard tissue characterization, positions CMR as the ideal imaging modality for&#xD;
        comprehensively characterizing FMR and the underlying myopathic processes that significantly&#xD;
        impact response to FMR therapies. The goal of the current research is to develop personalized&#xD;
        risk prediction for FMR patients through explainable unsupervised phenomapping enriched with&#xD;
        advanced CMR imaging biomarkers, and to determine the CMR predictors of reverse remodeling&#xD;
        following modern therapies for FMR.&#xD;
  &#xD;
        The proposed research will leverage a large retrospective single center NICM CMR database.&#xD;
        Our CMR NICM database currently features 458 NICM patients, who underwent CMR on a single CMR&#xD;
        vendor platform from 2008-2017, who have been extensively curated with contoured data for&#xD;
        standard CMR measures. An additional 802 NICM patients have been identified from our&#xD;
        2018-2021 CMR database with EF&lt;50% with the same inclusion/exclusion criteria, which will be&#xD;
        extensively curated to enable phenomapping discovery. An external 400 NICM patient cohort&#xD;
        will be used as an external validation cohort.&#xD;
  &#xD;
        The prospective study entails aiming to recruit 360 adult patients (ages &gt;18 years) with EF&#xD;
        10-50% and FMR RF&gt; 20%, who are clinically referred for CMR evaluation. Patients who enroll&#xD;
        in our study will be referred for optimization of mGDMT with Heart Failure Pharmacist Clinic&#xD;
        and followed every 2 weeks until optimized. All will return and undergo follow-up CMR studies&#xD;
        at 6months. NICM patients who are fully medically optimized with significant FMR at the time&#xD;
        of the baseline CMR and are referred for Mitraclip treatment will undergo follow-up CMR 6&#xD;
        months from Mitraclip intervention. NICM patients referred for mGDMT optimization, but have&#xD;
        persistent or progressive FMR at the time of 6 month follow-up CMR and referred for Mitraclip&#xD;
        therapy, will undergo a 2nd follow-up CMR 6 months from Mitraclip therapy. CMR will be done&#xD;
        on dedicated cardiac research MRI scanner.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 1, 2023</start_date>
    <completion_date type="Anticipated">December 31, 2028</completion_date>
    <primary_completion_date type="Anticipated">December 31, 2028</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>Composite of cardiac mortality, heart transplant, or LVAD implantation.</measure>
      <time_frame>Up to 36 months</time_frame>
      <description>Occurrence of cardiac mortality and/or heart transplant and/or LVAD implantation</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Change in FMR</measure>
      <time_frame>6 months</time_frame>
      <description>a change of &gt;5 units/percentage points compared to baseline</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in NT-proBNP</measure>
      <time_frame>6 months</time_frame>
      <description>30% change in NT-proBNP or decrease to level &lt; 1000 compared to baseline</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in KCQL score</measure>
      <time_frame>6 months</time_frame>
      <description>5 point change in KCQL score compared to baseline</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in 6-minute walk test</measure>
      <time_frame>6 months</time_frame>
      <description>25 meter change in 6-minute walk test compared to baseline</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Recurrent heart failure hospitalization</measure>
      <time_frame>up to 1 year</time_frame>
      <description>Occurrence of heart failure related hospitalization</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Arrhythmias</measure>
      <time_frame>up to 1 year</time_frame>
      <description>Occurrence of arrhythmia</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>MI</measure>
      <time_frame>up to 1 year</time_frame>
      <description>Occurrence of myocardial infarction</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Stroke</measure>
      <time_frame>up to 1 year</time_frame>
      <description>Occurrence of stroke</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Heart transplant</measure>
      <time_frame>up to 1 year</time_frame>
      <description>Occurrence of heart transplant</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>LVAD implantation</measure>
      <time_frame>up to 1 year</time_frame>
      <description>Occurrence of implant of left ventricular assisted device (LVAD)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Mortality</measure>
      <time_frame>up to 1 year</time_frame>
      <description>Occurrence of mortality</description>
    </secondary_outcome>
    <number_of_groups>2</number_of_groups>
    <enrollment type="Anticipated">360</enrollment>
    <condition>Nonischemic Congestive Cardiomyopathy</condition>
    <condition>Functional Mitral Regurgitation</condition>
    <arm_group>
      <arm_group_label>Optimize mGDMT</arm_group_label>
      <description>NICM patients referred for mGDMT optimization</description>
    </arm_group>
    <arm_group>
      <arm_group_label>MitraClip and mGDMT</arm_group_label>
      <description>NICM patients who are fully medically optimized with significant FMR at the time of the baseline CMR and are referred for Mitraclip treatment</description>
    </arm_group>
    <intervention>
      <intervention_type>Diagnostic Test</intervention_type>
      <intervention_name>Cardiac magnetic resonance (CMR)</intervention_name>
      <description>Cardiac magnetic resonance (CMR) at 6 months. If referred to MitraClip, CMR will be performed at 6 months from the procedure.</description>
      <arm_group_label>MitraClip and mGDMT</arm_group_label>
      <arm_group_label>Optimize mGDMT</arm_group_label>
    </intervention>
    <biospec_retention>Samples With DNA</biospec_retention>
    <biospec_descr>
      <textblock>
        Blood&#xD;
      </textblock>
    </biospec_descr>
    <eligibility>
      <study_pop>
        <textblock>
          Patients referred to Cleveland Clinic Structural Interventional Cardiology Clinic for&#xD;
          evaluation of possible percutaneous MV intervention are routinely referred for CMR as part&#xD;
          of their clinical protocol, and will be recruited for this prospective study. Additionally,&#xD;
          patients clinically referred for CMR for evaluation of cardiomyopathy, who are found to&#xD;
          have FMR RF &gt;20% for enrollment into this prospective study.&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
          1 CMR LVEF &lt;50% 2.FMR Fraction&gt;20%, with adequate image quality and no evidence of severe&#xD;
          obstructive CAD&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. &gt;moderate aortic regurgitation/stenosis,&#xD;
  &#xD;
            2. &lt;18 years of age,&#xD;
  &#xD;
            3. acute myocarditis,&#xD;
  &#xD;
            4. eGFR&lt;15&#xD;
  &#xD;
            5. HCM&#xD;
  &#xD;
            6. cardiac amyloidosis/sarcoidosis&#xD;
  &#xD;
            7. prior mitral valve intervention&#xD;
  &#xD;
            8. myocardial infarction within 8 weeks of CMR&#xD;
  &#xD;
            9. ischemic infarct pattern on CMR&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
    </eligibility>
    <overall_official>
      <last_name>Deborah Kwon, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>The Cleveland Clinic</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Deborah Kwon, MD</last_name>
      <phone>216-444-8526</phone>
      <email>kwond@ccf.org</email>
    </overall_contact>
    <location>
      <facility>
        <name>Cleveland Clinic</name>
        <address>
          <city>Cleveland</city>
          <state>Ohio</state>
          <zip>44195</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Deborah Kwon, MD</last_name>
        <phone>216-444-8526</phone>
        <email>kwond@ccf.org</email>
      </contact>
      <investigator>
        <last_name>Samir Kapadia, MD</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Wilson Tang, MD</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>David Chen, PhD</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Xiaofeng Wang, PhD</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Marc Gillinov, MD</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Christopher Nguyen, PhD</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Nancy Obuchowski, PhD</last_name>
        <role>Sub-Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 20, 2023</study_first_submitted>
    <study_first_submitted_qc>July 20, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">July 28, 2023</study_first_posted>
    <last_update_submitted>July 28, 2023</last_update_submitted>
    <last_update_submitted_qc>July 28, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 1, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>The Cleveland Clinic</investigator_affiliation>
      <investigator_full_name>Deborah Kwon, MD</investigator_full_name>
      <investigator_title>Principal Investigator</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Cardiomyopathies</mesh_term>
      <mesh_term>Mitral Valve Insufficiency</mesh_term>
      <mesh_term>Cardiomyopathy, Dilated</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05965258
  org study id: 23-702
  secondary id: 1R01HL170090-01
  nct id: NCT05965258
  lead sponsor: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  The goal of the current research is to develop personalized risk prediction for functional
        mitral regurgitation (FMR) patients through explainable unsupervised phenomapping enriched
        with advanced cardiac magnetic resonance (CMR) imaging biomarkers, and to determine the CMR
        predictors of reverse remodeling following modern therapies for FMR.
  
        The prospective study entails aiming to recruit 360 adult patients (ages >18 years) with EF
        10-50% and FMR RF> 20%, who are clinically referred for CMR evaluation. Patients who enroll
        in our study will be referred for optimization of mGDMT and will undergo follow-up CMR
        studies at 6months. NICM patients who are fully medically optimized with significant FMR at
        the time of the baseline CMR and are referred for Mitraclip treatment will undergo follow-up
        CMR 6 months from Mitraclip intervention. NICM patients referred for mGDMT optimization, but
        have persistent or progressive FMR at the time of 6 month follow-up CMR and referred for
        Mitraclip therapy, will undergo a 2nd follow-up CMR 6 months from Mitraclip therapy.
  Functional mitral regurgitation (FMR) portends a bleak prognosis and is a common consequence
        of ischemic and non-ischemic cardiomyopathy (ICM, NICM), where adverse annular and left
        ventricular (LV) remodeling and/or infarction alters mitral valve (MV) function.
  
        Prior studies demonstrate significant increases in mortality risk as severity of FMR
        increases; mortality rates range from 15-40% at 1 year. Furthermore, as the prevalence of
        heart failure (HF) is rising, FMR is projected to double from over 2 million patients in 2000
        to over 4 million patients in the United States by 2030. Defining FMR severity, optimal
        timing of intervention, and most appropriate method for intervention remain controversial.
        Recently, MITRA-FR and COAPT trials demonstrated contrasting survival benefit with
        percutaneous MV repair, demonstrating the importance and need for more optimal selection
        criteria. Currently, the patient selection criteria for Mitraclip therapy are solely based on
        MV anatomy and controversial echocardiographic criteria for FMR severity. Cardiac magnetic
        resonance (CMR) provides an exciting opportunity to address numerous unmet needs regarding
        characterizing FMR and the need for more optimal selection criteria for improving outcomes.
        Superior accuracy and reproducibility for quantification of LV size and function, and gold
        standard tissue characterization, positions CMR as the ideal imaging modality for
        comprehensively characterizing FMR and the underlying myopathic processes that significantly
        impact response to FMR therapies. The goal of the current research is to develop personalized
        risk prediction for FMR patients through explainable unsupervised phenomapping enriched with
        advanced CMR imaging biomarkers, and to determine the CMR predictors of reverse remodeling
        following modern therapies for FMR.
  
        The proposed research will leverage a large retrospective single center NICM CMR database.
        Our CMR NICM database currently features 458 NICM patients, who underwent CMR on a single CMR
        vendor platform from 2008-2017, who have been extensively curated with contoured data for
        standard CMR measures. An additional 802 NICM patients have been identified from our
        2018-2021 CMR database with EF<50% with the same inclusion/exclusion criteria, which will be
        extensively curated to enable phenomapping discovery. An external 400 NICM patient cohort
        will be used as an external validation cohort.
  
        The prospective study entails aiming to recruit 360 adult patients (ages >18 years) with EF
        10-50% and FMR RF> 20%, who are clinically referred for CMR evaluation. Patients who enroll
        in our study will be referred for optimization of mGDMT with Heart Failure Pharmacist Clinic
        and followed every 2 weeks until optimized. All will return and undergo follow-up CMR studies
        at 6months. NICM patients who are fully medically optimized with significant FMR at the time
        of the baseline CMR and are referred for Mitraclip treatment will undergo follow-up CMR 6
        months from Mitraclip intervention. NICM patients referred for mGDMT optimization, but have
        persistent or progressive FMR at the time of 6 month follow-up CMR and referred for Mitraclip
        therapy, will undergo a 2nd follow-up CMR 6 months from Mitraclip therapy. CMR will be done
        on dedicated cardiac research MRI scanner.
  observational model: Cohort
  time perspective: Prospective
  measure: Composite of cardiac mortality, heart transplant, or LVAD implantation.
  time frame: Up to 36 months
  description: Occurrence of cardiac mortality and/or heart transplant and/or LVAD implantation
  measure: Change in FMR
  time frame: 6 months
  description: a change of >5 units/percentage points compared to baseline
  measure: Change in NT-proBNP
  time frame: 6 months
  description: 30% change in NT-proBNP or decrease to level < 1000 compared to baseline
  measure: Change in KCQL score
  time frame: 6 months
  description: 5 point change in KCQL score compared to baseline
  measure: Change in 6-minute walk test
  time frame: 6 months
  description: 25 meter change in 6-minute walk test compared to baseline
  measure: Recurrent heart failure hospitalization
  time frame: up to 1 year
  description: Occurrence of heart failure related hospitalization
  measure: Arrhythmias
  time frame: up to 1 year
  description: Occurrence of arrhythmia
  measure: MI
  time frame: up to 1 year
  description: Occurrence of myocardial infarction
  measure: Stroke
  time frame: up to 1 year
  description: Occurrence of stroke
  measure: Heart transplant
  time frame: up to 1 year
  description: Occurrence of heart transplant
  measure: LVAD implantation
  time frame: up to 1 year
  description: Occurrence of implant of left ventricular assisted device (LVAD)
  measure: Mortality
  time frame: up to 1 year
  description: Occurrence of mortality
  arm group label: Optimize mGDMT
  description: NICM patients referred for mGDMT optimization
  arm group label: MitraClip and mGDMT
  description: NICM patients who are fully medically optimized with significant FMR at the time of the baseline CMR and are referred for Mitraclip treatment
  intervention type: Diagnostic Test
  intervention name: Cardiac magnetic resonance (CMR)
  description: Cardiac magnetic resonance (CMR) at 6 months. If referred to MitraClip, CMR will be performed at 6 months from the procedure.
  arm group label: MitraClip and mGDMT
  arm group label: Optimize mGDMT
  Blood
  study pop: 
  sampling method: Probability Sample
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  last name: Deborah Kwon, MD
  role: Principal Investigator
  affiliation: The Cleveland Clinic
  last name: Deborah Kwon, MD
  phone: 216-444-8526
  email: kwond@ccf.org
  facility: 
  contact: 
  investigator: 
  investigator: 
  investigator: 
  investigator: 
  investigator: 
  investigator: 
  investigator: 
  country: United States
  responsible party type: Principal Investigator
  investigator affiliation: The Cleveland Clinic
  investigator full name: Deborah Kwon, MD
  investigator title: Principal Investigator
  mesh term: Cardiomyopathies
  mesh term: Mitral Valve Insufficiency
  mesh term: Cardiomyopathy, Dilated
  sharing ipd: No