The Effect of Angiotensin Receptor-Neprilysin Inhibition on Cardiac Fibrosis in Patients With HFpEF

Heart Failure With Preserved Ejection Fraction Clinical Trial

— ARNICFH  

Official title:

The Effect of Angiotensin Receptor-Neprilysin Inhibition on Cardiac Fibrosis in Patients With HFpEF: A Randomized Controlled Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05089539
• Other study ID #: 2021-10-21
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: November 1, 2021
• Est. completion date: April 1, 2022

Study information

• Verified date: October 2021
• Source: Chongqing Medical University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The effectively therapeutic approaches for Heart failure with preserved ejection fraction (HFpEF) remain limited. The PARAGON-HF trial found that Angiotensin Receptor-Neprilysin Inhibition (ARNI) has potential benefits for the management of HFpEF. Nevertheless, the role of ARNI in cardiac fibrosis in HFpEF are still unclear. We will conduct a prospective randomized controlled trial to evaluate the effect of ARNI on cardiac fibrosis in patients with HFpEF by cardiac magnetic resonance (CMR).

Description:

Heart failure with preserved ejection fraction (HFpEF) comprises approximately 50% of all heart failure. The effectively therapeutic approaches for HFpEF remain limited. The PARAGON-HF trial found that Angiotensin Receptor-Neprilysin Inhibition (ARNI) has potential benefits for the management of HFpEF. Nevertheless, the role of ARNI in cardiac fibrosis in HFpEF are still unclear. We will conduct a prospective randomized controlled trial to evaluate the effect of ARNI on cardiac fibrosis in patients with HFpEF by cardiac magnetic resonance (CMR). We will randomly assign 60 patients with HFpEF (NYHA II-IV) class, ejection fraction ≥ 50% and elevated level of natriuretic peptides to receive sacubitril-valsartan (target 100mg bid) or placebo (100mg bid). The primary endpoint is change in extracellular volume [ECV] measured by CMR. The secondary endpoints were 6-minute walking distance(6-WMD), KCCQ, hospitalizations for heart failure, myocardial infarction and death.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 60
• Est. completion date: April 1, 2022
• Est. primary completion date: February 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 45 Years and older

Eligibility

Inclusion Criteria:

• Signed and dated written informed consent
• Age = 45 years at time of screening
• Preserved systolic left ventricular function, defined by left ventricular ejection fraction (LVEF) = 50%
• NYHA classes II-IV
• H2FPEF score = 6 or HFA-PEFF score = 5

Exclusion Criteria:

• Patients with a known history of angioedema
• History of hypersensitivity to ARNI
• Any prior echocardiographic measurement of LVEF <45%
• Significant congenital heart disease
• Rheumatic valvular heart disease
• Acute coronary syndrome, cardiac surgery, other major cardiovascular surgery
• Probable alternative diagnoses could account for the patient's HF symptoms
• Systolic blood pressure(BP) >180 mm Hg or diastolic BP >120 mm Hg at visit
• Diastolic BP <90 mm Hg at visit 1, or symptomatic hypotension
• Patients with a cardiac pacemaker therapy device
• eGFR <30 ml/min/1.73 m2
• Serum potassium >5.2 mmol/l at visit 1
• Pregnant or nursing women

Related Conditions & MeSH terms

• Fibrosis
• Heart Failure
• Heart Failure With Preserved Ejection Fraction

Intervention

Drug:
• Angiotensin Receptor-Neprilysin Inhibition
Sacubitril/valsartan [100 mg] bid). Continuous treatment was maintained for at least three months.
• Placebo
Placebo [100 mg] bid). Continuous treatment was maintained for at least three months.

Locations

Country	Name	City	State
China	The first affiliated Hospital of Chongqing Medical University	Chongqing

Sponsors (1)

Lead Sponsor	Collaborator
Chongqing Medical University

Country where clinical trial is conducted

China, 

References & Publications (3)

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, Düngen 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 Investigators and Committees. Angiotensin-Neprilysin Inhibition in Heart Failure with Preserved Ejection Fraction. N Engl J Med. 2019 Oct 24;381(17):1609-1620. doi: 10.1056/NEJMoa1908655. Epub 2019 Sep 1. — View Citation

Vaduganathan M, Jhund PS, Claggett BL, Packer M, Widimský J, Seferovic P, Rizkala A, Lefkowitz M, Shi V, McMurray JJV, Solomon SD. A putative placebo analysis of the effects of sacubitril/valsartan in heart failure across the full range of ejection fraction. Eur Heart J. 2020 Jul 1;41(25):2356-2362. doi: 10.1093/eurheartj/ehaa184. — View Citation

van der Meer P, Gaggin HK, Dec GW. ACC/AHA Versus ESC Guidelines on Heart Failure: JACC Guideline Comparison. J Am Coll Cardiol. 2019 Jun 4;73(21):2756-2768. doi: 10.1016/j.jacc.2019.03.478. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Extracellular volume [ECV]	Extracellular volume [ECV] assessment by CMR	Before ARNI or placebo treatment and after 3 months of continuous ANRI or palcebo treatment
Secondary	myocardial infarction, hospitalization for heart failure and death	myocardial infarction, hospitalization for heart failure and all-cause death	After 3 months of continuous ANRI or palcebo treatment