Heart Failure With Moderately Reduced Ejection FractionPhase 3CRACOVIA-HFNCT05508035
The Effect of Sacubitril/Valsartan Versus Ramipril on Left Ventricular Function and Remodeling in Patients With Ischemic Heart Failure With Mid-range Ejection Fraction
A Phase 3 study testing Sacubitril / Valsartan and Ramipril in people with Heart Failure With Moderately Reduced Ejection Fraction, run by John Paul II Hospital, Krakow at 1 site in Poland.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure With Moderately Reduced Ejection Fraction
- What is being tested?
- Sacubitril / Valsartan and Ramipril
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 488 participants
- Where
- 1 sitePoland
- Study dates
- 13 Jul 2023to Dec 2028
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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 resynchronization therapy device incompatible with MRI.
- Fixed atrial fibrillation.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Poland1 site, 1 recruiting
- Recruiting
Krakowski Szpital Specjalistyczny im. św. Jana Pawła II
Krakow, Lesser Poland Voivodeship, 31-202
+48789459021, cracovia-hf@szpitaljp2.krakow.pl
About this study
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.
Read more
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.
- Being tested
- Sacubitril / Valsartan, Ramipril
- Keywords
- chronic heart failure, congestive heart failure
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sacubitril / ValsartanDrug
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.
RamiprilDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| sacubitril / valsartan | Experimental | sacubitril / valsartan 200 mg twice a day PLUS placebo for ramipril 5 mg twice a day Receives: Drug: Sacubitril / Valsartan |
| ramipril | Active comparator | ramipril 5 mg twice a day PLUS placebo for sacubitril / valsartan 200 mg twice a day Receives: Drug: Ramipril |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 12 months
Secondary outcomes (10)
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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Aug 2022
- Study start13 Jul 2023
- Primary completionAug 2028 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart Failure With Moderately Reduced Ejection FractionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 488 participants (estimated)
Sponsor and investigators
- Lead sponsor
- John Paul II Hospital, Krakow
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05508035
- Sponsor's protocol ID
- DW.0701.005.2020P
- Acronym
- CRACOVIA-HF
- Status last verified
- Jul 2026
- First submitted
- 11 Aug 2022
- Last updated
- 31 Jul 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No