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

Heart Failure With Preserved Ejection Fraction Clinical Trial

— PRAISE-MR  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05991284
• Other study ID #: Z-2023036
• Status: Recruiting
• Phase: Phase 4
• Start date: February 14, 2024
• Est. completion date: April 1, 2026

Study information

• Verified date: August 2023
• Source: Ziekenhuis Oost-Limburg
• Contact: Philippe Bertrand, MD, PhD
• Phone: 089/32 71 40
• Email: philippe.bertrand[@]zol.be
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 110
• Est. completion date: April 1, 2026
• Est. primary completion date: September 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 95 Years

Eligibility

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.

Related Conditions & MeSH terms

• Functional Mitral Regurgitation
• Heart Failure
• Heart Failure With Preserved Ejection Fraction
• Mitral Valve Insufficiency

Intervention

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

Locations

Country	Name	City	State
Belgium	Ziekenhuis Oost-Limburg	Genk

Sponsors (2)

Lead Sponsor	Collaborator
Ziekenhuis Oost-Limburg	Jessa Hospital

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in mean pulmonary arterial pressure over cardiac output slope assessed by CPETecho		Six months of treatment
Secondary	Change in peak oxygen uptake		Six months of treatment
Secondary	Change in mitral effective regurgitant orifice area (EROA)		Six months of treatment
Secondary	Change in natriuretic peptide levels		Six months of treatment
Secondary	Change in left atrial volume (LAVI)		Six months of treatment
Secondary	Change the minute ventilation over carbon dioxide production slope		Six months of treatment
Secondary	Change in patient reported outcomes (Kansas City Cardiomyopathy Questionnaire, KCCQ-12)		Six months of treatment
Secondary	Change in left atrial function (peak atrial longitudinal strain, PALS)		Six months of treatment