The Effect of Sacubitril/valsartan Versus Ramipril on Left Ventricular Function and Remodeling in Patients with Ischemic Heart Failure with Mid-range Ejection Fraction

Summary

Heart failure with moderately reduced ejection fraction (HFmrEF) is a frequent disease associated with significant morbidity and mortality and therefore requires effective therapies that may improve clinical outcomes. The most common reason of HFmrEF is ischemic injury, usually caused by myocardial infarction, that may lead to left ventricular remodeling and systolic dysfunction, accompanied by symptoms of heart failure. Therefore, the anti-remodeling therapies may effectively improve clinical outcomes. Recently, sacubitril/valsartan - the angiotensin receptor neprilysin inhibitor suppressing the renin-angiotensin-aldosterone system and enhancing the effect of natriuretic peptides - has been introduced in the treatment of heart failure. To date, this drug was found to be clinically beneficial in patients with heart failure with reduced ejection fraction (HFrEF), however has not been tested in the group of patients with HFmrEF.

The aim of the study is to evaluate effectiveness of sacubitril/valsartan as compared with ramipril on left ventricular remodeling and function in patients with ischemic HFmrEF.

Patients with ischemic HFmrEF, New York Heart Association class II-IV symptoms, an elevated plasma natriuretic peptide level and the left ventricular ejection fraction (LVEF) of 40-49 % will be enrolled in this prospective, multicenter, randomized, double-blind, active-controlled study. Initially, patients will enter a single-blind ramipril run-in period (titrated to 5 mg bid), followed by a sacubitril/valsartan run-in period (100 mg titrated to 200 mg bid). A total of 666 patients tolerating both periods will be randomized 1:1 to either ramipril 10 mg bid or sacubitril/valsartan 200 mg bid. The primary endpoint will be the change of left ventricular end-systolic volume index within 12-month of treatment as measured by magnetic resonance imaging. The main secondary endpoints include the change of left ventricular end-diastolic volume index within 12-month of treatment, the change of LVEF within 12-month of treatment, 12-month composite endpoint of cardiovascular death or heart failure requiring hospitalization, 12-month cardiovascular death, 12-month heart failure requiring hospitalization, time to death or heart failure requiring hospitalization or mortality rate within 12-month of treatment.

This study may determine the place of sacubitril/valsartan as an alternative to ramipril in the treatment of patients with ischemic HFmrEF in order to prevent further left ventricular remodeling and to improve its systolic function.

Conditions

• Heart Failure with Moderately Reduced Ejection Fraction

Interventions

DRUG

Sacubitril / Valsartan

The participants will be randomized to either ramipril 5 mg twice daily plus placebo for sacubitril / valsartan 200 mg twice daily or sacubitril / valsartan 200 mg twice daily plus placebo for ramipril 5 mg twice daily in 1: 1 ratio using the IT randomization module. All patients eligible for randomization will receive their first dose of double-blind drug plus placebo the day after randomization visit. After assigning a randomized treatment, patients will continue at the target dose and attend a 2-week telephone follow-up followed by site visits after one month, four months, eight months and in the final visit after 12 months.

DRUG

Ramipril

The participants will be randomized to either ramipril 5 mg twice daily plus placebo for sacubitril / valsartan 200 mg twice daily or sacubitril / valsartan 200 mg twice daily plus placebo for ramipril 5 mg twice daily in 1: 1 ratio using the IT randomization module. All patients eligible for randomization will receive their first dose of double-blind drug plus placebo the day after randomization visit. After assigning a randomized treatment, patients will continue at the target dose and attend a 2-week telephone follow-up followed by site visits after one month, four months, eight months and in the final visit after 12 months.

Sponsors & Collaborators

• John Paul II Hospital, Krakow

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-07-13

Primary Completion

2027-03-31

Completion

2027-06-30

Countries

• Poland

Study Locations