NCT06536309

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

• Status: Not Yet Recruiting
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 36 (estimated)
• Sponsor: Brigham and Women's Hospital · Academic / Other
• Sex: All
• Age: 50 Years – 85 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Heart Failure With Preserved Ejection Fraction
• Myocardial Fibrosis

Interventions

Type	Name	Description
DRUG	Sacubitril-valsartan	Sacubitril-valsartan titrated to maximally targeted dose
DRUG	Valsartan	Valsartan titrated to maximally targeted dose

Timeline

• Start date: 2026-07-01
• Primary completion: 2028-12-01
• Completion: 2029-09-01
• First posted: 2024-08-02
• Last updated: 2026-02-25

Regulatory

• FDA-regulated drug study