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Sacubitril-Valsartan in Heart Failure With Preserved Ejection Fraction and Secondary Mitral Valve Regurgitation (PRAISE-MR)

Primary Purpose

Heart Failure With Preserved Ejection Fraction, Functional Mitral Regurgitation

Status
Not yet recruiting
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
Sacubitril-valsartan
Standard of care
Sponsored by
Ziekenhuis Oost-Limburg
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Heart Failure With Preserved Ejection Fraction

Eligibility Criteria

18 Years - 95 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Age > 18 years. New York Heart Association class II to IV. Written informed consent. Left ventricular (LV) ejection fraction ≥ 50%. Objective evidence of cardiac structural and/or functional abnormalities consistent with the presence of LV diastolic dysfunction/raised LV filling pressures, including raised natriuretic peptides. ≥ moderate functional MR assessed by transthoracic echocardiography within the previous year. Exclusion Criteria: Systolic blood pressure < 100 mmHg. Potassium ≥ 5.2 mmol/L. Estimated Glomerular Filtration Rate ≤ 25 ml/min/1.73m². History of angioedema or unacceptable side effects during receipt of angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARB). Structural mitral valve disease and previous or planned mitral valve intervention. Already receiving angiotensin receptor neprilysin inhibitor (ARNI, sacubitril-valsartan) therapy. Severe comorbid condition limiting life expectancy < 24 months or inability to perform a maximal CPETecho. Myocardial infarction, unstable angina, coronary revascularization within 12 weeks prior enrolment. Severe aortic, tricuspid or pulmonary valve disease. Pregnancy, lactation, or use of any method of contraception that is not highly effective.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Active Comparator

    Placebo Comparator

    Arm Label

    Intervention arm

    Control arm

    Arm Description

    Sacubitril-Valsartan (target dose 97/103 mg twice daily) on top of standard of care (including SGLT-2 inhibitor and MRA)

    Standard of care (including SGLT-2 inhibitor and MRA)

    Outcomes

    Primary Outcome Measures

    Change in mean pulmonary arterial pressure over cardiac output slope assessed by CPETecho

    Secondary Outcome Measures

    Change in peak oxygen uptake
    Change in mitral effective regurgitant orifice area (EROA)
    Change in natriuretic peptide levels
    Change in left atrial volume (LAVI)
    Change the minute ventilation over carbon dioxide production slope
    Change in patient reported outcomes (Kansas City Cardiomyopathy Questionnaire, KCCQ-12)
    Change in left atrial function (peak atrial longitudinal strain, PALS)

    Full Information

    First Posted
    August 1, 2023
    Last Updated
    August 10, 2023
    Sponsor
    Ziekenhuis Oost-Limburg
    Collaborators
    Jessa Hospital
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05991284
    Brief Title
    Sacubitril-Valsartan in Heart Failure With Preserved Ejection Fraction and Secondary Mitral Valve Regurgitation
    Acronym
    PRAISE-MR
    Official Title
    Sacubitril-Valsartan in Heart Failure With Preserved Ejection Fraction and Secondary Mitral Valve Regurgitation
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    August 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    September 1, 2023 (Anticipated)
    Primary Completion Date
    September 1, 2025 (Anticipated)
    Study Completion Date
    April 1, 2026 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Ziekenhuis Oost-Limburg
    Collaborators
    Jessa Hospital

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Product Manufactured in and Exported from the U.S.
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    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).

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Heart Failure With Preserved Ejection Fraction, Functional Mitral Regurgitation

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 4
    Interventional Study Model
    Parallel Assignment
    Model Description
    Multicenter, Investigator-initiated, Prospective, Randomized trial with Open Blinded Endpoint
    Masking
    Outcomes Assessor
    Masking Description
    Blinded core echocardiography laboratory
    Allocation
    Randomized
    Enrollment
    110 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Intervention arm
    Arm Type
    Active Comparator
    Arm Description
    Sacubitril-Valsartan (target dose 97/103 mg twice daily) on top of standard of care (including SGLT-2 inhibitor and MRA)
    Arm Title
    Control arm
    Arm Type
    Placebo Comparator
    Arm Description
    Standard of care (including SGLT-2 inhibitor and MRA)
    Intervention Type
    Drug
    Intervention Name(s)
    Sacubitril-valsartan
    Intervention Description
    sacubitril-valsartan (target dose 97/103 mg twice daily)
    Intervention Type
    Drug
    Intervention Name(s)
    Standard of care
    Intervention Description
    including SGLT-2 inhibitor and MRA
    Primary Outcome Measure Information:
    Title
    Change in mean pulmonary arterial pressure over cardiac output slope assessed by CPETecho
    Time Frame
    Six months of treatment
    Secondary Outcome Measure Information:
    Title
    Change in peak oxygen uptake
    Time Frame
    Six months of treatment
    Title
    Change in mitral effective regurgitant orifice area (EROA)
    Time Frame
    Six months of treatment
    Title
    Change in natriuretic peptide levels
    Time Frame
    Six months of treatment
    Title
    Change in left atrial volume (LAVI)
    Time Frame
    Six months of treatment
    Title
    Change the minute ventilation over carbon dioxide production slope
    Time Frame
    Six months of treatment
    Title
    Change in patient reported outcomes (Kansas City Cardiomyopathy Questionnaire, KCCQ-12)
    Time Frame
    Six months of treatment
    Title
    Change in left atrial function (peak atrial longitudinal strain, PALS)
    Time Frame
    Six months of treatment

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    95 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Age > 18 years. New York Heart Association class II to IV. Written informed consent. Left ventricular (LV) ejection fraction ≥ 50%. Objective evidence of cardiac structural and/or functional abnormalities consistent with the presence of LV diastolic dysfunction/raised LV filling pressures, including raised natriuretic peptides. ≥ moderate functional MR assessed by transthoracic echocardiography within the previous year. Exclusion Criteria: Systolic blood pressure < 100 mmHg. Potassium ≥ 5.2 mmol/L. Estimated Glomerular Filtration Rate ≤ 25 ml/min/1.73m². History of angioedema or unacceptable side effects during receipt of angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARB). Structural mitral valve disease and previous or planned mitral valve intervention. Already receiving angiotensin receptor neprilysin inhibitor (ARNI, sacubitril-valsartan) therapy. Severe comorbid condition limiting life expectancy < 24 months or inability to perform a maximal CPETecho. Myocardial infarction, unstable angina, coronary revascularization within 12 weeks prior enrolment. Severe aortic, tricuspid or pulmonary valve disease. Pregnancy, lactation, or use of any method of contraception that is not highly effective.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Philippe Bertrand, MD, PhD
    Phone
    089/32 71 40
    Email
    philippe.bertrand@zol.be
    First Name & Middle Initial & Last Name or Official Title & Degree
    Sebastiaan Dhont, MD
    Phone
    +32471626094
    Email
    sebastiaan.dhont@zol.be

    12. IPD Sharing Statement

    Plan to Share IPD
    No

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    Sacubitril-Valsartan in Heart Failure With Preserved Ejection Fraction and Secondary Mitral Valve Regurgitation

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