Date

2026-01-27

Protocol

Protocol changed

Item Changed

Exclusion criteria

Previous Version

1. Diagnosis of type 1 diabetes or prior history of diabetic ketoacidosis 2. Documented prior history of severe hyperkalemia in the setting of MRA use 3. Treatment with non-steroidal mineralocorticoid receptor antagonist (MRA) or SGLT2i 4. 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 5. Prior or planned heart transplant 6. Hemodynamically significant uncorrected primary cardiac valvular disease as primary cause of heart failure 7. 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 8. Probable alternative cause of participant's heart failure symptoms 9. Concomitant systemic therapy with potent cytochrome P450 isoenzyme 3A4 (CYP3A4) inhibitors or moderate CYP3A4 inducers, or potent CYP3A4 inducers 10. 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. 11. Concurrent participation in another interventional clinical study using an investigational agent within 30 days prior to randomization.

Next Version

1. Diagnosis of type 1 diabetes or prior history of diabetic ketoacidosis. 2. Documented prior history of severe hyperkalemia (potassium ?6.0 mmol/L and/or resulting in hospitalization or Emergency Department visit) in the setting of MRA use. 3. Currently on or planned for long-term therapy with non-steroidal MRA (finerenone, esaxerenone, apararenone, balcinrenone), steroidal MRA (spironolactone, eplerenone, canrenone), or SGLT2i. Potential participants should not have MRA or SGLT2i stopped for the purpose of enrollment into the study. Patients with recent MRA exposure should not be randomized or receive study treatment until 7 days from the last dose to allow adequate washout. 4. eGFR 5.0 mmol/L at screening. 5. Acute MI due to plaque rupture4, coronary revascularization, valve replacement/repair, or implantation of a cardiac resynchronization therapy device within 30 days prior to randomization. (Note: pacemakers or implantable cardioverter defibrillators without resynchronization function are allowed.) 6. Prior heart transplant or listed for heart transplant with expectation to receive a transplant during the course of this trial (according to investigator judgement) or currently using or plan for mechanical circulatory support, e.g., left ventricular assist device, intra-aortic balloon pump, or patients on mechanical ventilation or patients with planned outpatient inotropic support. 7. Hemodynamically significant (severe) uncorrected primary cardiac valvular disease considered by the investigator to be the primary cause of HF. (Note: secondary mitral regurgitation or tricuspid regurgitation due to dilated cardiomyopathy is not excluded unless planned for surgery or intervention during the course of the study.) 8. Cardiomyopathy due to known acute inflammatory heart disease (e.g., acute myocarditis within 90 days prior to randomization), infiltrative diseases (e.g., amyloidosis), accumulation diseases (e.g., haemochromatosis, Fabry disease), muscular dystrophies, cardiomyopathy with reversible causes (e.g., stress cardiomyopathy), known hypertrophic obstructive cardiomyopathy, complex (according to investigator`s judgement) congenital heart disease, or known pericardial constriction. 9. Probable alternative cause of participant’s HF symptoms that, in the opinion of the investigator, primarily accounts for patient’s symptoms; specifically, patients with severe pulmonary disease requiring home oxygen or chronic oral steroid therapy, primary pulmonary arterial hypertension at screening. 10. Concomitant systemic therapy with potent cytochrome P450 isoenzyme 3A4 (CYP3A4) inhibitors (e.g., itraconazole, ritonavir, indinavir, cobicistat, clarithromycin), or moderate CYP3A4 inducers (e.g., efavirenz, phenobarbital), or potent CYP3A4 inducers (e.g., carbamazepine, phenytoin, St. John’s Wort) that cannot be discontinued 7 days prior to randomization and for the duration of the treatment period. (Note: a list of excluded CYP3A4 inhibitors and inducers is provided in Appendix D.) Concomitant treatment with renin inhibitor, more than one angiotensin converting enzyme inhibitor (ACEi), angiotensin receptor blocker (ARB) or ARNI, or with a potassium-sparing diuretic that cannot be stopped prior to randomization and for the duration of the treatment period. 11. Known hypersensitivity to finerenone or empagliflozin (active substance or excipients). 12. Any other condition or therapy (e.g., breastfeeding, cardiogenic shock, clinically overt severe hepatic insufficiency [Child Pugh C], Addison’s disease, or other severe condition as per investigator’s judgment such as disease with