A Phase 3 interventional study of Sacubitril / Valsartan and Ramipril in Heart Failure With Moderately Reduced Ejection Fraction, sponsored by John Paul II Hospital, Krakow. Recruiting at 1 site in Poland. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-07-31.
Sponsored by John Paul II Hospital, Krakow · Phase 3, Interventional, and Treatment
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.
6,331 studies on the registry are indexed under Heart Failure; 1,396 are open to participants now.
This study's planned enrollment of 488 is above the median of 76 across 4,049 interventional studies indexed under Heart Failure.
Browse Heart Failure studies →John Paul II Hospital, Krakow is the lead sponsor of 16 studies on the registry; 6 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.
Stroke symptoms need emergency care at once, even if they go away.
NYHA class (heart failure)
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
LVEF (left ventricular ejection fraction)
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Creatinine clearance (CrCl)
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
TIA (transient ischaemic attack)
A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.
Stroke symptoms need emergency care at once, even if they go away.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
sacubitril / valsartan 200 mg twice a day PLUS placebo for ramipril 5 mg twice a day
Drug: Sacubitril / Valsartan
ramipril 5 mg twice a day PLUS placebo for sacubitril / valsartan 200 mg twice a day
Drug: Ramipril
Drug pages: 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.
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.
Change in left ventricular end-systolic volume
Assessment of the effect of sacubitril / valsartan versus ramipril on the change in left ventricular end-systolic volume as measured by MRI in patients with ischemic HFmrEF
Time frame: 12 months
Change in left ventricular end-diastolic volume
Assessment of the effect of sacubitril / valsartan versus ramipril on the change in left ventricular end-diastolic volume as measured by MRI in patients with ischemic HFmrEF
Time frame: 12 months
Change in indexed left ventricular end-systolic and end-diastolic volumes
Assessment of the effect of sacubitril / valsartan versus ramipril on the change in indexed left ventricular end-systolic and end-diastolic volumes as measured by MRI in patients with ischemic HFmrEF
Time frame: 12 months
Change in left ventricular ejection fraction
Assessment of the effect of sacubitril / valsartan versus ramipril on the change in left ventricular ejection fraction as measured by MRI in patients with ischemic HFmrEF
Time frame: 12 months
Occurrence of the endpoint of death from cardiovascular causes or first hospitalization for HF
Assessment of the effect of sacubitril / valsartan versus ramipril on the occurrence of the endpoint of death from cardiovascular causes or first hospitalization for HF in patients with ischemic HFmrEF
Time frame: 12 months
Occurrence of the endpoint of death from cardiovascular causes or first or subsequent hospitalization for HF
Assessment of the effect of sacubitril / valsartan versus ramipril on the occurrence of the endpoint of death from cardiovascular causes or first or subsequent hospitalization for HF in patients with ischemic HFmrEF
Time frame: 12 months
Occurrence of death from cardiovascular causes
Assessment of the effect of sacubitril / valsartan versus ramipril on the occurrence of death from cardiovascular causes in patients with ischemic HFmrEF
Time frame: 12 months
First hospitalization due to HF
Assessment of the effect of sacubitril / valsartan versus ramipril on the first hospitalization due to HF in patients with ischemic HFmrEF
Time frame: 12 months
Occurrence of the first or subsequent hospitalization due to HF
Assessment of the effect of sacubitril / valsartan versus ramipril on the occurrence of the first or subsequent hospitalization due to HF in patients with ischemic HFmrEF
Time frame: 12 months
Time to death from cardiovascular causes or first hospitalization for HF
Assessment of the effect of sacubitril / valsartan versus ramipril on the time to death from cardiovascular causes or first hospitalization for HF in patients with ischemic HFmrEF
Time frame: 12 months
Occurrence of death from any cause
Assessment of the effect of sacubitril / valsartan versus ramipril on the occurrence of death from any cause in patients with ischemic HFmrEF
Time frame: 12 months
Incidence of hypotension
Incidence of symptomatic hypotension and/or hypotension with systolic blood pressure \<95 mmHg in patients on sacubitril / valsartan versus in those on ramipril
Time frame: 12 months
Occurrence of hyperkalaemia
Assessment of the effect of sacubitril / valsartan versus ramipril on the occurrence of hyperkalaemia (\>5.4 mmol/L)
Time frame: 12 months
Onset or worsening of renal failure
Assessment of the effect of sacubitril / valsartan versus ramipril on the onset or worsening of renal failure (eGFR \<30 ml / minute / 1.73 m2 or decrease in eGFR compared to visit W1 or W2 by more than 25%)
Time frame: 12 months
Started Jul 2023 (actual). Primary completion is estimated for Aug 2028, 61 months after the start.
Of 88 non-industry phase 3 interventional studies under Heart Failure, half reached primary completion within 50 months of starting (the median), counting those still running; a quarter within 28 and three quarters within 63. This study's planned 61 months is above that.
Counting every sponsor, half of 151 studies reached it within 39 months; a quarter within 25 and three quarters within 57.
How these figures are worked out, and which studies are left out of them.
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Studies of the drugs tested here: Sacubitril · Valsartan
John Paul II Hospital, Krakow