RecruitingPhase 3

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

Poland488 participantsStarted 2023-07-13

Plain-language 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.

Who can participate

Age range

18 Years

Sex

ALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion Criteria: * Written consent to participate in the study, expressed prior to any procedures related to the study. * Age 18 and over. * Symptomatic HF in NYHA class II to IV of ischemic etiology. * Left ventricular ejection fraction at screening visit ranged from 40-49%. * Elevated concentration of NT-proBNP natriuretic peptide ≥125 pg/ml. * Features of a structural / functional disease of the left ventricle. * Optimal pharmacotherapy with ACEI or ARB and beta-blocker, unless they are contraindicated. Exclusion Criteria: * History of hypersensitivity or allergy to any of the drugs tested or drugs of similar chemical class, ACEIs, ARBs or neprilysin inhibitors. * Previous history of intolerance to recommended ACEI or ARB target doses. * Known history of angioedema. * Requirement of simultaneous treatment with ACEI and ARB. * Acute decompensated HF within 6 weeks prior to screening visit. * Symptomatic hypotension systolic blood pressure \<100 mmHg at screening visit. * Current or previous treatment with sacubitril / valsartan. * Estimated creatinine clearance \<30 ml / min / 1.73 m2 at screening visit. * Serum potassium \>5.2 mmol / L at screening visit. * Acute coronary syndrome or elective revascularization within 6 weeks prior to screening. * Stroke, transient ischemic attack, carotid angioplasty, heart surgery, or any other major cardiovascular surgery in the 3 months prior to screening. * Implantation of a cardioverter defibrillator, pacemaker, or resynchroniza…

Questions worth asking your doctor

Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.

1This trial is comparing sacubitril/valsartan to ramipril specifically for heart failure with a mid-range ejection fraction — is my ejection fraction in that range, and does that make me a potential candidate worth discussing with you?
2The trial is measuring changes in left ventricular end-systolic volume as its main outcome — can you explain what that means for my heart function, and why it matters whether one drug shrinks or changes the heart's size more than the other?
3Since this is a Phase 3 trial comparing two real medications rather than a placebo, what are the known risks of each drug, and how does being in this trial compare to just starting one of them as a standard treatment today?
4Ramipril is already a well-established medication for heart failure — what would I potentially be giving up or gaining by enrolling in this trial instead of simply starting ramipril or another guideline-recommended therapy right now?
5This trial is still actively recruiting, so if I were interested in discussing enrollment with you, what would the practical demands look like — things like how often I'd need to come in for visits or tests to track my heart volume over time?

Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.

Questions for the trial coordinator

The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.

1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?

A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.

What they're measuring

Change in left ventricular end-systolic volume

Timeframe: 12 months

Trial details

NCT IDNCT05508035

SponsorJohn Paul II Hospital, Krakow

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2028-08

Contact for this trial

Jadwiga Nessler, professor

+48 12 6142218 badaniakliniczne@szpitaljp2.krakow.pl

View on ClinicalTrials.gov More Heart Failure With Moderately Reduced Ejection Fraction trials