Clinical trial NCT05089539: The Effect of Angiotensin Receptor-Neprilysin Inhibition on Cardiac Fibrosis in Patients With HFpEF
Official title: The Effect of Angiotensin Receptor-Neprilysin Inhibition on Cardiac Fibrosis in Patients With HFpEF: A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Heart Failure With Preserved Ejection Fraction
Lead sponsor: Chongqing Medical University
Sponsor class: OTHER
First posted: 2021-10-22
Enrollment: 60
Sex: ALL
Minimum age (years): 45
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Extracellular volume [ECV]
timeFrame: Before ARNI or placebo treatment and after 3 months of continuous ANRI or palcebo treatment
Secondary outcomes:
measure: myocardial infarction, hospitalization for heart failure and death
timeFrame: After 3 months of continuous ANRI or palcebo treatment
Other outcomes:
Locations:
city: Chongqing
country: China
facility: The first affiliated Hospital of Chongqing Medical University
Study officials:
References:
citation: 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 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.
citation: Vaduganathan M, Jhund PS, Claggett BL, Packer M, Widimsky 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.
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.