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

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).

Study Overview

• Status: Recruiting
• Conditions: Heart Failure With Preserved Ejection Fraction; Functional Mitral Regurgitation
• Intervention / Treatment: Drug: Sacubitril-valsartan; Drug: Standard of care

• Study Type: Interventional
• Enrollment (Estimated): 110
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Philippe Bertrand, MD, PhD; Phone Number: 089/32 71 40; Email: philippe.bertrand@zol.be
• Study Contact Backup: Name: Sebastiaan Dhont, MD; Phone Number: +32471626094; Email: sebastiaan.dhont@zol.be

Study Locations

• Belgium
  • Genk, Belgium, 3600
    • Recruiting
    • Ziekenhuis Oost-Limburg
    • Contact: Philippe Bertrand, MD, PhD; Email: Philippe.Bertrand@zol.be

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Intervention arm; Sacubitril-Valsartan (target dose 97/103 mg twice daily) on top of standard of care (including SGLT-2 inhibitor and MRA)	Drug: Sacubitril-valsartan; sacubitril-valsartan (target dose 97/103 mg twice daily); Drug: Standard of care; including SGLT-2 inhibitor and MRA
Placebo Comparator: Control arm; Standard of care (including SGLT-2 inhibitor and MRA)	Drug: Standard of care; including SGLT-2 inhibitor and MRA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in mean pulmonary arterial pressure over cardiac output slope assessed by CPETecho	Six months of treatment

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Ziekenhuis Oost-Limburg
• Collaborators: Jessa Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): February 14, 2024
• Primary Completion (Estimated): September 1, 2025
• Study Completion (Estimated): April 1, 2026

Study Registration Dates

• First Submitted: August 1, 2023
• First Submitted That Met QC Criteria: August 10, 2023
• First Posted (Actual): August 14, 2023

Study Record Updates

• Last Update Posted (Actual): January 29, 2024
• Last Update Submitted That Met QC Criteria: January 25, 2024
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Valve Diseases; Heart Failure; Mitral Valve Insufficiency; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Valsartan; Sacubitril and valsartan sodium hydrate drug combination
• Other Study ID Numbers: Z-2023036

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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