Not Yet RecruitingPhase 4

Neprilysin Inhibition to Reduce Myocardial Fibrosis in Heart Failure With Preserved Ejection Fraction

36 participantsStarted 2026-07

Plain-language summary

Cardiac magnetic resonance imaging (MRI) measures of myocardial interstitial fibrosis (MIF) are elevated in heart failure with preserved ejection fraction (HFpEF) patients and associated with poor prognosis. Extracellular volume (ECV) is the most reproducible and best validated cardiac MRI measure of MIF. Sacubitril/valsartan reduces histological MIF in mice and levels of some extracellular matrix regulatory proteins in humans with HFpEF. However, the effect of sacubitril/valsartan on robust measures of MIF in humans is unknown. Demonstrating reductions in ECV with sacubitril/valsartan would clarify the mechanism of this approved medication. Given the borderline reduction in heart failure hospitalizations with sacubitril/valsartan and the heterogeneity of HFpEF pathophysiology, this result would suggest that neprilysin inhibition may particularly benefit HFpEF patients with greater MIF. The investigators propose a proof-of-concept clinical trial to evaluate the effect of neprilysin inhibition (sacubitril/valsartan vs valsartan alone) on cardiac MRI measures of fibrosis (principally ECV) and circulating protein levels.

Who can participate

Age range

50 Years – 85 Years

Sex

ALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion Criteria: * Adults aged 50 years or older * Able to provide informed consent, as assessed by a physician investigator, and willing to comply with the study * Clinically confirmed diagnosis of heart failure * Left ventricular ejection fraction greater than or equal to 45% within 1 year by echocardiogram, cardiac MRI, or nuclear scan Exclusion Criteria: * Contraindication to MRI (metal prosthesis, implantable cardiac device, or severe claustrophobia) * Systolic blood pressure \< 100mm Hg, or \<110 mm Hg for patients not taking an ACE inhibitor or angiotensin receptor blocker * symptomatic hypotension * eGFR \< 30 mL/min/1.73m2 within 60 days of enrollment * Serum potassium \>5.2mmol/L within 60 days of enrollment, or \>5.0 mmol/L for patients not taking an ACE inhibitor or angiotensin receptor blocker * Myocardial infarction within 6 months of enrollment * Infiltrative or hypertrophic cardiomyopathy * History of cirrhosis, biliary cirrhosis, or cholestasis * History of angioedema * Pregnancy, planning pregnancy, or breastfeeding * Active treatment with lithium or a direct renin inhibitor

Questions worth asking your doctor

Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.

1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?

Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.

Questions for the trial coordinator

The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.

1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?

A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.

What they're measuring

Change in extracellular volume by cardiac MRI

Timeframe: 1 year

Trial details

NCT IDNCT06536309

SponsorBrigham and Women's Hospital

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2028-12

Contact for this trial

Jonathan Cunningham, MD

671-732-5524 jcunningham3@bwh.harvard.edu

View on ClinicalTrials.gov More Heart Failure With Preserved Ejection Fraction trials