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

ConditionsHeart Failure With Preserved Ejection Fraction Myocardial Fibrosis

Trial statusNot yet recruiting

Trial phasePhase 4

Trial typeInterventional

Biological sexAll

Age50-85

SponsorBrigham and Women's Hospital

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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

Trial design

Design model

Parallel

Treatments tested in this trial

Sacubitril-valsartan
Drug
Sacubitril-valsartan titrated to maximally targeted dose
Valsartan
Drug
Valsartan titrated to maximally targeted dose

Treatment groups

36 Participants

are divided into 2 treatment groups

Group A: Sacubitril/valsartanExperimental treatment 1 intervention

Group B: ValsartanActive comparator 1 intervention

Trial outcomes

Primary outcomes

Change in extracellular volume by cardiac MRI

The primary outcome is to evaluate the change in extracellular volume (ECV), measured by cardiac MRI, from baseline to one year, in the sacubitril/valsartan arm compared to the valsartan arm

Time frame

1 year

Secondary outcomes

Change in left ventricular native T1 time

Measured by cardiac MRI

Time frame

1 year

Other outcomes

Change in left ventricular mass

Measured by cardiac MRI

Time frame

1 year

Change in left atrial size

Time frame

1 year

Locations

This trial has no locations.

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Brigham and Women's Hospital

Lead sponsor

Source ClinicalTrials.gov

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