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/NCT05991284</url>
    </required_header>
    <id_info>
      <org_study_id>Z-2023036</org_study_id>
      <nct_id>NCT05991284</nct_id>
    </id_info>
    <brief_title>Sacubitril-Valsartan in Heart Failure With Preserved Ejection Fraction and Secondary Mitral Valve Regurgitation</brief_title>
    <acronym>PRAISE-MR</acronym>
    <official_title>Sacubitril-Valsartan in Heart Failure With Preserved Ejection Fraction and Secondary Mitral Valve Regurgitation</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Ziekenhuis Oost-Limburg</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Jessa Hospital</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Ziekenhuis Oost-Limburg</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>
      <is_us_export>No</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        The main objective of this study is to assess the hemodynamic effects of sacubitril-valsartan&#xD;
        in patients with heart failure with preserved ejection fraction and at least moderate atrial&#xD;
        functional mitral regurgitation (AFMR), using a combination of cardiopulmonary exercise&#xD;
        testing and stress echocardiography (referred to as CPETecho) at baseline and after six&#xD;
        months of therapy. The patients included in this study will be randomly assigned to receive&#xD;
        sacubitril-valsartan as an adjunct to standard medical care, as opposed to adhering solely to&#xD;
        the standard of care which involves sodium-glucose cotransporter-2 (SGLT-2) inhibitor and&#xD;
        mineralocorticoid receptor antagonist (MRA).&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 1, 2023</start_date>
    <completion_date type="Anticipated">April 1, 2026</completion_date>
    <primary_completion_date type="Anticipated">September 1, 2025</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>
      <intervention_model_description>Multicenter, Investigator-initiated, Prospective, Randomized trial with Open Blinded Endpoint</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Single (Outcomes Assessor)</masking>
      <masking_description>Blinded core echocardiography laboratory</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>Change in mean pulmonary arterial pressure over cardiac output slope assessed by CPETecho</measure>
      <time_frame>Six months of treatment</time_frame>
    </primary_outcome>
    <secondary_outcome>
      <measure>Change in peak oxygen uptake</measure>
      <time_frame>Six months of treatment</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in mitral effective regurgitant orifice area (EROA)</measure>
      <time_frame>Six months of treatment</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in natriuretic peptide levels</measure>
      <time_frame>Six months of treatment</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in left atrial volume (LAVI)</measure>
      <time_frame>Six months of treatment</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change the minute ventilation over carbon dioxide production slope</measure>
      <time_frame>Six months of treatment</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in patient reported outcomes (Kansas City Cardiomyopathy Questionnaire, KCCQ-12)</measure>
      <time_frame>Six months of treatment</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in left atrial function (peak atrial longitudinal strain, PALS)</measure>
      <time_frame>Six months of treatment</time_frame>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">110</enrollment>
    <condition>Heart Failure With Preserved Ejection Fraction</condition>
    <condition>Functional Mitral Regurgitation</condition>
    <arm_group>
      <arm_group_label>Intervention arm</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Sacubitril-Valsartan (target dose 97/103 mg twice daily) on top of standard of care (including SGLT-2 inhibitor and MRA)</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Control arm</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>Standard of care (including SGLT-2 inhibitor and MRA)</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Sacubitril-valsartan</intervention_name>
      <description>sacubitril-valsartan (target dose 97/103 mg twice daily)</description>
      <arm_group_label>Intervention arm</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Standard of care</intervention_name>
      <description>including SGLT-2 inhibitor and MRA</description>
      <arm_group_label>Control arm</arm_group_label>
      <arm_group_label>Intervention arm</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Age &gt; 18 years.&#xD;
  &#xD;
            -  New York Heart Association class II to IV.&#xD;
  &#xD;
            -  Written informed consent.&#xD;
  &#xD;
            -  Left ventricular (LV) ejection fraction ≥ 50%.&#xD;
  &#xD;
            -  Objective evidence of cardiac structural and/or functional abnormalities consistent&#xD;
               with the presence of LV diastolic dysfunction/raised LV filling pressures, including&#xD;
               raised natriuretic peptides.&#xD;
  &#xD;
            -  ≥ moderate functional MR assessed by transthoracic echocardiography within the&#xD;
               previous year.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Systolic blood pressure &lt; 100 mmHg.&#xD;
  &#xD;
            -  Potassium ≥ 5.2 mmol/L.&#xD;
  &#xD;
            -  Estimated Glomerular Filtration Rate ≤ 25 ml/min/1.73m².&#xD;
  &#xD;
            -  History of angioedema or unacceptable side effects during receipt of angiotensin&#xD;
               converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARB).&#xD;
  &#xD;
            -  Structural mitral valve disease and previous or planned mitral valve intervention.&#xD;
  &#xD;
            -  Already receiving angiotensin receptor neprilysin inhibitor (ARNI,&#xD;
               sacubitril-valsartan) therapy.&#xD;
  &#xD;
            -  Severe comorbid condition limiting life expectancy &lt; 24 months or inability to perform&#xD;
               a maximal CPETecho.&#xD;
  &#xD;
            -  Myocardial infarction, unstable angina, coronary revascularization within 12 weeks&#xD;
               prior enrolment.&#xD;
  &#xD;
            -  Severe aortic, tricuspid or pulmonary valve disease.&#xD;
  &#xD;
            -  Pregnancy, lactation, or use of any method of contraception that is not highly&#xD;
               effective.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>95 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Philippe Bertrand, MD, PhD</last_name>
      <phone>089/32 71 40</phone>
      <email>philippe.bertrand@zol.be</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Sebastiaan Dhont, MD</last_name>
      <phone>+32471626094</phone>
      <email>sebastiaan.dhont@zol.be</email>
    </overall_contact_backup>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 1, 2023</study_first_submitted>
    <study_first_submitted_qc>August 10, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 14, 2023</study_first_posted>
    <last_update_submitted>August 10, 2023</last_update_submitted>
    <last_update_submitted_qc>August 10, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 14, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <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>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Valsartan</mesh_term>
      <mesh_term>Sacubitril and valsartan sodium hydrate drug combination</mesh_term>
    </intervention_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/NCT05991284
  org study id: Z-2023036
  nct id: NCT05991284
  lead sponsor: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  is us export: No
  The main objective of this study is to assess the hemodynamic effects of sacubitril-valsartan
        in patients with heart failure with preserved ejection fraction and at least moderate atrial
        functional mitral regurgitation (AFMR), using a combination of cardiopulmonary exercise
        testing and stress echocardiography (referred to as CPETecho) at baseline and after six
        months of therapy. The patients included in this study will be randomly assigned to receive
        sacubitril-valsartan as an adjunct to standard medical care, as opposed to adhering solely to
        the standard of care which involves sodium-glucose cotransporter-2 (SGLT-2) inhibitor and
        mineralocorticoid receptor antagonist (MRA).
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: Multicenter, Investigator-initiated, Prospective, Randomized trial with Open Blinded Endpoint
  primary purpose: Treatment
  masking: Single (Outcomes Assessor)
  masking description: Blinded core echocardiography laboratory
  measure: Change in mean pulmonary arterial pressure over cardiac output slope assessed by CPETecho
  time frame: Six months of treatment
  measure: Change in peak oxygen uptake
  time frame: Six months of treatment
  measure: Change in mitral effective regurgitant orifice area (EROA)
  time frame: Six months of treatment
  measure: Change in natriuretic peptide levels
  time frame: Six months of treatment
  measure: Change in left atrial volume (LAVI)
  time frame: Six months of treatment
  measure: Change the minute ventilation over carbon dioxide production slope
  time frame: Six months of treatment
  measure: Change in patient reported outcomes (Kansas City Cardiomyopathy Questionnaire, KCCQ-12)
  time frame: Six months of treatment
  measure: Change in left atrial function (peak atrial longitudinal strain, PALS)
  time frame: Six months of treatment
  arm group label: Intervention arm
  arm group type: Active Comparator
  description: Sacubitril-Valsartan (target dose 97/103 mg twice daily) on top of standard of care (including SGLT-2 inhibitor and MRA)
  arm group label: Control arm
  arm group type: Placebo Comparator
  description: Standard of care (including SGLT-2 inhibitor and MRA)
  intervention type: Drug
  intervention name: Sacubitril-valsartan
  description: sacubitril-valsartan (target dose 97/103 mg twice daily)
  arm group label: Intervention arm
  intervention type: Drug
  intervention name: Standard of care
  description: including SGLT-2 inhibitor and MRA
  arm group label: Control arm
  arm group label: Intervention arm
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 95 Years
  healthy volunteers: No
  last name: Philippe Bertrand, MD, PhD
  phone: 089/32 71 40
  email: philippe.bertrand@zol.be
  last name: Sebastiaan Dhont, MD
  phone: +32471626094
  email: sebastiaan.dhont@zol.be
  responsible party type: Sponsor
  mesh term: Heart Failure
  mesh term: Mitral Valve Insufficiency
  mesh term: Valsartan
  mesh term: Sacubitril and valsartan sodium hydrate drug combination
  sharing ipd: No