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

NCT05991284 — Phase 4, Completed, 84 participants, Ziekenhuis Oost-Limburg

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Registry	NCT05991284, acronym PRAISE-MR
Status	Completed
Phase	Phase 4
Study type	Interventional; randomized, parallel, masking: single, treatment
Enrollment	84 (Actual)
Sponsor	Ziekenhuis Oost-Limburg (Other); collaborators: Jessa Hospital
Conditions	Heart Failure With Preserved Ejection Fraction, Functional Mitral Regurgitation
Interventions	Sacubitril-valsartan, Standard of care (Drug)
Dates	start 2024-02-29, primary completion 2025-09-22, completion 2026-05-09, first posted 2023-08-14, last updated 2026-06-08
Locations	1 site in Belgium

-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).

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+Arms and interventions

Arm	Type	Interventions	Description
Intervention arm	Active comparator	Drug: Sacubitril-valsartan; Drug: Standard of care	Sacubitril-Valsartan (target dose 97/103 mg twice daily) on top of standard of care (including SGLT-2 inhibitor and MRA)
Control arm	Placebo comparator	Drug: Standard of care	Standard of care (including SGLT-2 inhibitor and MRA)

Sacubitril-valsartan (Drug): sacubitril-valsartan (target dose 97/103 mg twice daily)
Standard of care (Drug): including SGLT-2 inhibitor and MRA

+Outcome measures

Primary outcomes

Change in mean pulmonary arterial pressure over cardiac output slope assessed by CPETecho [Six months of treatment]

Secondary outcomes

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]

+Eligibility

Sex: All, ages: 18 Years to 95 Years

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.

+Locations (1)

Facility	City	Country	Status
Ziekenhuis Oost-Limburg	Genk	Belgium

+Publications

Results publication: Dhont S, Moura Ferreira S, Galloo X, Martens P, Meekers E, Tartaglia K, Deferm S, Herbots L, Mullens W, Verbrugge FH, Verwerft J, Bertrand PB. Angiotensin Receptor Neprilysin Inhibitor in Heart Failure With Preserved Ejection Fraction and Secondary Mitral Regurgitation: The PRAISE-MR Randomized Trial. Circulation. 2026 Jun 23;153(25):1973-1983. doi: 10.1161/CIRCULATIONAHA.126.080833. Epub 2026 May 9. PMID 42104906