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Not yet recruiting NCT06536309

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

Phase IV Interventional Heart Failure With Preserved Ejection Fraction Myocardial Fibrosis

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: Sacubitril-valsartan, Valsartan.
Who it may be relevant to
Registry conditions: Heart Failure With Preserved Ejection Fraction, Myocardial Fibrosis. Basic parameters: 50 years — 85 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
Center list to be confirmed — check the primary protocol.
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Overview

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.

Interventions

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

Primary outcome measures

  • Change in extracellular volume by cardiac MRI [Time frame: 1 year]
Secondary outcome measures (1)
  • Change in left ventricular native T1 time [Time frame: 1 year]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
Randomized
Model
Parallel assignment
Masking
Quadruple blind
Primary purpose
Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Publications

  • Solomon SD, McMurray JJV, Anand IS, Ge J, Lam CSP, Maggioni AP, Martinez F, Packer M, Pfeffer MA, Pieske B, Redfield MM, Rouleau JL, van Veldhuisen DJ, Zannad F, Zile MR, Desai AS, Claggett B, Jhund PS, Boytsov SA, Comin-Colet J, Cleland J, Dungen HD, Goncalvesova E, Katova T, Kerr Saraiva JF, Lelonek M, Merkely B, Senni M, Shah SJ, Zhou J, Rizkala AR, Gong J, Shi VC, Lefkowitz MP; PARAGON-HF Inve PMID 31475794

Identifiers

NCT: NCT06536309 · 2024P001894 · 1K23HL168163-01A1

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗