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

Phase 4

Recruiting

• Conditions: Heart Failure with Preserved Ejection Fraction; Functional Mitral Regurgitation
• Interventions: Drug: Sacubitril-valsartan; Drug: Standard of care

• Registration Number: NCT05991284
• Lead Sponsor: Ziekenhuis Oost-Limburg

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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-08-01
• Study First Submitted QC: 2023-08-10
• Study First Posted: 2023-08-14
• Study Start: 2024-02-29
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-22
• Last Update Posted: 2025-01-27
• Primary Completion: 2026-09-01
• Study Completion: 2026-12-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 110

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intervention arm	Standard of care	Sacubitril-Valsartan (target dose 97/103 mg twice daily) on top of standard of care (including SGLT-2 inhibitor and MRA)
Intervention arm	Sacubitril-valsartan	Sacubitril-Valsartan (target dose 97/103 mg twice daily) on top of standard of care (including SGLT-2 inhibitor and MRA)
Control arm	Standard of care	Standard of care (including SGLT-2 inhibitor and MRA)

Primary Outcome Measures

Name	Time	Method
Change in mean pulmonary arterial pressure over cardiac output slope assessed by CPETecho	Six months of treatment

Secondary Outcome Measures

Name	Time	Method
Change in left atrial volume (LAVI)	Six months of treatment
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 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
Change the minute ventilation over carbon dioxide production slope	Six months of treatment

Trial Locations

Locations (1)

Ziekenhuis Oost-Limburg; 🇧🇪 Genk, Belgium