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

Sponsor

Ziekenhuis Oost-Limburg (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05991284

Collaborator

Jessa Hospital (Other)

110

Enrollment

Arms

Anticipated Duration (Months)

Study Details

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).

Condition or Disease	Intervention/Treatment	Phase
Heart Failure With Preserved Ejection Fraction Functional Mitral Regurgitation	Drug: Sacubitril-valsartan Drug: Standard of care	Phase 4

Study Design

Study Type:

Interventional

Anticipated Enrollment :

110 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Multicenter, Investigator-initiated, Prospective, Randomized trial with Open Blinded EndpointMulticenter, Investigator-initiated, Prospective, Randomized trial with Open Blinded Endpoint

Masking:

Single (Outcomes Assessor)

Masking Description:

Blinded core echocardiography laboratory

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Sep 1, 2023

Anticipated Primary Completion Date :

Sep 1, 2025

Anticipated Study Completion Date :

Apr 1, 2026

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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 Criteria

Criteria

Ages Eligible for Study:

18 Years to 95 Years

Sexes Eligible for Study:

All

Accepts 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.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

Ziekenhuis Oost-Limburg
Jessa Hospital

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Ziekenhuis Oost-Limburg

ClinicalTrials.gov Identifier:

NCT05991284

Other Study ID Numbers:

Z-2023036

First Posted:

Aug 14, 2023

Last Update Posted:

Aug 14, 2023

Last Verified:

Aug 1, 2023

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Additional relevant MeSH terms:

Heart Failure

Mitral Valve Insufficiency

Valsartan

Sacubitril and valsartan sodium hydrate drug combination

Study Results

No Results Posted as of Aug 14, 2023