Clinical trial NCT05991284: Sacubitril-Valsartan in Heart Failure with Preserved Ejection Fraction and Secondary Mitral Valve Regurgitation
Official title: Sacubitril-Valsartan in Heart Failure with Preserved Ejection Fraction and Secondary Mitral Valve Regurgitation
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Heart Failure with Preserved Ejection Fraction
Functional Mitral Regurgitation
Lead sponsor: Ziekenhuis Oost-Limburg
Sponsor class: OTHER
Collaborators: name: Jessa Hospital
First posted: 2023-08-14
Enrollment: 110
Sex: ALL
Minimum age (years): 18
Maximum age (years): 95
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multicenter, Investigator-initiated, Prospective, Randomized trial with Open Blinded Endpoint
Primary purpose: TREATMENT

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).


Eligibility criteria: 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.

Primary outcomes:
measure: Change in mean pulmonary arterial pressure over cardiac output slope assessed by CPETecho
timeFrame: Six months of treatment
Secondary outcomes:
measure: Change in peak oxygen uptake
timeFrame: Six months of treatment
measure: Change in mitral effective regurgitant orifice area (EROA)
timeFrame: Six months of treatment
measure: Change in natriuretic peptide levels
timeFrame: Six months of treatment
measure: Change in left atrial volume (LAVI)
timeFrame: Six months of treatment
measure: Change the minute ventilation over carbon dioxide production slope
timeFrame: Six months of treatment
measure: Change in patient reported outcomes (Kansas City Cardiomyopathy Questionnaire, KCCQ-12)
timeFrame: Six months of treatment
measure: Change in left atrial function (peak atrial longitudinal strain, PALS)
timeFrame: Six months of treatment
Other outcomes:
Locations:
city: Genk
country: Belgium
facility: Ziekenhuis Oost-Limburg
Study officials:
References: