Heart Failure (HF) and reduced ejection fraction (HFrEF)
Conditions
Interventions
Study sites- National Hospital of Sri Lanka, Colombo North Teaching Hospital, Kandy National Hospital, Colombo South Teaching Hospital, Jaffna Teaching Hospital, Negombo District General Hospital.
Sponsors
Colorado Prevention Center - Clinical Research
Eligibility
Inclusion criteria
Inclusion criteria: 1. Provide electronic or written informed consent, either personally or through a legally authorized representative 2. Age >18 years or legal age of majority 3. Symptomatic HFrEF according to: a. NYHA class II-IV symptoms at screening and randomization. b. Ejection fraction <40% by imaging within 12 months prior to screening. c. Qualifying natriuretic peptide level: Most recent local laboratory value within 14 days of randomization for patients with recent HHF (discharged within prior 10 days) or within 30 days for patients without recent HHF must meet the qualifying threshold below. If no value is available in the medical record, a local lab value must be obtained. Note: for participants treated with an angiotensin receptor/neprilysin inhibitor (ARNI) in the previous 4 weeks prior to natriuretic peptide measurement, only NTproBNP values should be used 4. Not on sMRA (i.e., spironolactone, eplerenone or canrenone/potassium canrenoate) due to documented history of being either intolerant, contraindicated (e.g., due to eGFR <30 mL/min/1.73m2 ) or considered ineligible for treatment with sMRA . 5. Persons of childbearing potential can only be included in the study if a pregnancy test is negative at screening and if they agree to use adequate contraception which is consistent with local regulations regarding the methods for contraception2 for the duration of the study.
Exclusion criteria
Exclusion criteria: 1.Treatment with nsMRA (e.g., finerenone, esaxerenone, apararenone) within 30 days prior to randomization; treatment with any MRA should not be interrupted for the purpose of enrollment into the study. 2. Documented severe hyperkalemia (potassium >6.0 mmol/L) or related hospitalization/Emergency Department visit with MRA use. 3. Low eGFR or high potassium: eGFR 5.0 mmol/L at screening. 4. Acute MI, coronary revascularization, valve replacement/repair, or cardiac resynchronization therapy device implantation within 30 days before randomization or planned. 5. Prior heart transplant or listed for heart transplant, or use of mechanical circulatory support (e.g., left ventricular assist device, intra-aortic balloon pump, or participants on mechanical ventilation or participants with planned outpatient inotropic support). 6. Hemodynamically significant uncorrected primary cardiac valvular disease-causing heart failure. 7. Symptomatic bradycardia or second- or third-degree heart block without a pacemaker. 8. Cardiomyopathy due to acute inflammatory heart disease e.g., acute myocarditis within 90 days prior to randomization, infiltrative diseases, accumulation diseases, muscular dystrophies, reversible causes, hypertrophic obstructive cardiomyopathy, complex congenital heart disease, or pericardial constriction. 9. Alternative cause of HF symptoms: Severe pulmonary disease requiring home oxygen or chronic oral steroid therapy, primary pulmonary arterial hypertension. 10. Concomitant systemic therapy with potent CYP3A4 inhibitors or inducers that cannot be discontinued 7 days prior to randomization. 11. Known hypersensitivity to the investigational product (active substance or excipients). 12. Conditions like breastfeeding, cardiogenic shock, severe hepatic insufficiency, Addison’s disease, malignancy, or other severe conditions with <1 year life expectancy. 13 Concurrent or previous participation in another interventional clinical study using an investigational agent
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Time to first occurrence of cardiovascular (CV) death or HF event - Time to first CV death or HF event with finerenone compared to placebo. “HF event definition includes either a hospitalization for heart failure or an urgent visit for worsening HF requiring intravenous therapy (e.g., IV diuretics or vasoactive agents).” These are counted toward the primary composite endpoint (time to first event): • Cardiovascular death • HF event [Ongoing, up to ~30 months ] Number of serious adverse events - Serious adverse events (excluding efficacy endpoints) with finerenone compared to placebo. A Serious Adverse Event (SAE) is defined as any untoward medical occurrence that: • Results in death • Is life-threatening • Requires inpatient hospitalization or prolongation of existing hospitalization • Results in persistent or significant disability/incapacity • Is a congenital anomaly or birth defect • Or is otherwise considered medically important (i.e., may jeopardize the patient or require intervention to prevent one of the above outcomes) Serious Adverse Event Reporting “Investigators must report all serious adverse events from the time of informed consent through the end of study participation.” [Ongoing, up to ~30 months ] Number of adverse events leading to discontinuation of study drug - Number of adverse events leading to discontinuation of investigational product with finerenone compared to placebo. [Ongoing, up to ~30 months] | — |
Secondary
| Measure | Time frame |
|---|---|
| Timing and occurrence of total CV deaths and HF events - Timing and occurrence of total (first and subsequent) events of CV death and HF events and CV deaths with finerenone compared to placebo. [Ongoing, up to ~30 months ] Timing and occurrence of total HF events - Timing and occurrence of total (first and recurrent) HF events with finerenone compared to placebo. [Ongoing, up to ~30 months ] Change in Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ-TSS) from baseline to Month 6 - Change in KCCQ-TSS with finerenone compared to placebo. [ 180 days ] Time to CV death - Time to CV death with finerenone compared to placebo. [ Ongoing, up to ~30 months ] Time to all-cause death - Time to all-cause mortality with finerenone compared to placebo. [ Ongoing, up to ~30 months ] | — |
Countries
Croatia,Czech Republic,Greece,Hungary,Italy,Poland,Spain,Sri Lanka,United Kingdom
Contacts
Public ContactDr. Gamini Galappatthy
Consultant Cardiologist
Outcome results
None listed