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

NCT05991284 | Active Not Recruiting Phase 4

• 1 other identifier: Z-2023036
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 1

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).

Conditions

Heart Failure With Preserved Ejection Fraction; Functional Mitral Regurgitation

Outcome Measures

Primary Outcomes (1)

• Change in mean pulmonary arterial pressure over cardiac output slope assessed by CPETecho

  Six months of treatment

Secondary Outcomes (7)

• 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

Study Arms (2)

Intervention arm

ACTIVE COMPARATOR

Sacubitril-Valsartan (target dose 97/103 mg twice daily) on top of standard of care (including SGLT-2 inhibitor and MRA)

Drug: Sacubitril-valsartan; Drug: Standard of care

Control arm

PLACEBO COMPARATOR

Standard of care (including SGLT-2 inhibitor and MRA)

Drug: Standard of care

Interventions

Sacubitril-valsartan DRUG

sacubitril-valsartan (target dose 97/103 mg twice daily)

Intervention arm

Standard of care DRUG

including SGLT-2 inhibitor and MRA

Control arm; Intervention arm

Eligibility Criteria

• Age: 18 Years - 95 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ziekenhuis Oost-Limburg: lead
• Jessa Hospital: collaborator

Study Sites (1)

Ziekenhuis Oost-Limburg

Genk, 3600, Belgium

Location

MeSH Terms

Interventions

sacubitril and valsartan sodium hydrate drug combination; Standard of Care

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Blinded core echocardiography laboratory
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Multicenter, Investigator-initiated, Prospective, Randomized trial with Open Blinded Endpoint

Study Record Dates

• First Submitted: August 1, 2023
• First Posted: August 14, 2023
• Study Start: February 29, 2024
• Primary Completion: September 22, 2025
• Study Completion: May 1, 2026
• Last Updated: December 19, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)