Will a strategy of early, intensive combination therapy with finerenone and an SGLT2i provide superior clinical outcomes (defined as a hierarchical composite of all-cause mortality, heart failure events, and >5 point difference in change from baseline for Kansas City Cardiomyopathy Questionnaire – Total Symptom Score [KCCQ-TSS]) compared with local standard of care in patients hospitalized with heart failure?

Can an early, intensive combination therapy with finerenone and an SGLT2i reduce time to first event of all-cause mortality or HF events (hospitalization for HF or urgent visit due to HF), improve KCCQ-TSS (at 6 months), and reduce HF events at 90 days?

1. The study setting/ Study sites:
   • The National Hospital of Sri Lanka
   • Colombo North Teaching Hospital
   • Kandy National Hospital
   • Colombo South Teaching Hospital
   • Jaffna Teaching Hospital
   • Negombo District General Hospital
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2. This is an open-label study. Participants will be randomly assigned (1:1) to treatment groups (e.g., IP or standard of care) based on a computer-generated randomization schedule prepared before the study by or under the supervision of the sponsor statistician or delegate. Randomization will be balanced by using randomly permuted blocks for each site and stratified by country and LVEF (<40%, > 40%).

3. Intervention: Participants will be randomly allocated (1:1) to standard of care management or an early, intensive management strategy including finerenone and empagliflozin. The dose will be adjusted based on the patient’s kidney function and serum/plasma potassium.

Participants allocated to the early, intensive management strategy will receive empagliflozin 10 mg daily and finerenone once daily at a starting dose of 10 or 20 mg based on the local laboratory eGFR at baseline.

The investigator will titrate the finerenone dose once the participant has been on a stable dose for 28±7 days.

Participants who do not tolerate their starting dose of 20 mg may be down titrated at any point during the study, including between scheduled visits if required for safety reasons. Up titration of dose may be performed from Day 28 onward at any scheduled or unscheduled contact. eGFR and serum/plasma potassium will be checked 28±7 days after dose adjustment and at any other time deemed appropriate by the investigator.

Participants will be instructed to take one tablet of finerenone at approximately the same time each day, with a glass of water with or without food, and to take empagliflozin as specified on the label.

Tablets containing 10 mg and 20 mg finerenone will differ in size from 40 mg finerenone tablets.

Participants in the standard of care arm will be managed by their usual care providers who will receive a summary of HF (Heart Failure) guideline recommendations. Eligibility criteria were selected to define a study population at high risk for worsening HF events while excluding those who may be exposed to particular risks with the intervention.

Standard therapy given in place of placebo is dependent on the patients usual care.

Since the study is open label, no groups are blinded to the intervention.

• Provide electronic or written informed consent, either personally or through a legally authorized representative
• Age >18 years or legal age of majority
• Current hospitalization or recently discharged with the primary diagnosis of heart failure
• Heart failure signs and symptoms at the time of hospital admissionElevated N-terminal pro B-type natriuretic peptide (NTproBNP) >500 pg/ mL or B-type natriuretic peptide (BNP) >125 pg/mL according to the local lab for patients in sinus rhythm; or elevated NTproBNP >1500 pg/mL or BNP >375 pg/mL for patients with atrial fibrillation (AF), measured during the current hospitalization or in the 72 hours prior to hospital admission.
• Fulfillment of protocol defined stabilization criteria (if randomized during hospitalization)
• Treatment during the index hospitalization with at least 1 intravenous dose of a loop diuretic (e.g., furosemide, torsemide, bumetanide).
• Negative pregnancy test and agreement to use adequate contraception during trial (female participants only)

• Diagnosis of type 1 diabetes or prior history of diabetic ketoacidosis
• Documented prior history of severe hyperkalemia in the setting of MRA use
• Treatment with non-steroidal mineralocorticoid receptor antagonist (MRA) or SGLT2i
• Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m² and/or serum/plasma potassium >5.0 mmol/L • Acute myocardial infarction, coronary revascularization, valve replacement/repair, or implantation of a cardiac resynchronization therapy device within 30 days
• Prior or planned heart transplant
• Hemodynamically significant uncorrected primary cardiac valvular disease as primary cause of heart failure
• Cardiomyopathy due to acute inflammatory heart disease, infiltrative diseases, accumulation diseases, muscular dystrophies, cardiomyopathy with reversible causes, known hypertrophic obstructive cardiomyopathy, complex congenital heart disease, or pericardial constriction
• Probable alternative cause of participant's heart failure symptoms
• Concomitant systemic therapy with potent cytochrome P450 isoenzyme 3A4 (CYP3A4) inhibitors or moderate CYP3A4 inducers, or potent CYP3A4 inducers
• Known hypersensitivity to the IP
• Any other condition or therapy which would make the patient unsuitable for this study and not allow participation for the full planned study period.
• Concurrent participation in another interventional clinical study using an investigational agent within 30 days prior to randomization.