A Study to Test Whether Vicadrostat in Combination With Empagliflozin Helps People With Heart Failure

Inclusion criteria:

1. At least 18 years old and at least of the legal age of consent in countries where itis greater than 18 years

2. Signed and dated written informed consent in accordance with ICH-GCP and locallegislation prior to admission to the trial

3. Male or female participants. Women of childbearing potential (WOCBP) must be readyand able to use highly effective methods of birth control per InternationalConference on Harmonisation (ICH) M3 (R2) that result in a low failure rate of lessthan 1% per year when used consistently and correctly. A list of contraceptionmethods meeting these criteria and instructions on the duration of their use isprovided in the participant information

4. Chronic Heart failure (HF) diagnosed at least 3 months before Visit 1, and in NewYork Heart Association (NYHA) class II-IV at Visit 1, with left ventricular ejectionfraction (LVEF) ≥40% per local reading. A historical LVEF may be used if it wasmeasured within 12 months prior to Visit 1, or the LVEF may be measured after studyconsent has been obtained and before randomisation at Visit 2

5. Presence of structural heart abnormality (confirmed by any imaging modality; i.e.echocardiography at Visit 1, as defined by left ventricular hypertrophy or leftatrial enlargement). Historical imaging may be used if performed within 12 monthsprior to Visit 1, or imaging may be completed after study consent has been obtainedand before Visit 2

6. Elevated N-terminal pro-brain natriuretic peptide (NT-proBNP) at Visit 1, analysedat the central laboratory at Visit 1:

7. in participants with body mass index (BMI) <27 kg/m²: ≥300 pg/mL forparticipants without atrial fibrillation (Afib) or atrial flutter (Aflutter) (at Visit 1 electrocardiogram (ECG)) and ≥900 pg/mL for participants with Afibor Aflutter (at Visit 1 ECG)

8. in participants with BMI ≥27 kg/m² to <35 kg/m²: ≥220 pg/mL for participantswithout Afib or Aflutter (at Visit 1 ECG) and ≥660 pg/mL for participants withAfib or Aflutter (at Visit 1 ECG)

9. in participants with BMI ≥35 kg/m²: ≥125 pg/mL for participants without Afib orAflutter (at Visit 1 ECG) and ≥375 pg/mL for participants with Afib or Aflutter (at Visit 1 ECG)

10. At least one of the following:

• Currently treated with diuretic therapy e.g. loop diuretics or thiazides, andon a stable dose for at least 1 week prior to Visit 1

• Documented hospitalisation for HF within 6 months prior to Visit 1

• Elevated NT-proBNP at Visit 1, analysed at the central laboratory at Visit 1

• in participants without Afib or Aflutter (at Visit 1 ECG): ≥900 pg/mL

• for participants with Afib or Aflutter (at Visit 1 ECG): ≥1800 pg/mL

• Urine albumin-to-creatinine ratio (UACR) ≥30 mg/g, analysed at the centrallaboratory at Visit 1

8. Treated according to best possible standard of care (SOC) (disregardingSodium-dependent glucose co-transporter 2 inhibitors (SGLT2is) and Mineralocorticoidreceptor antagonists (MRAs)) in accordance with applicable HF local/internationalguidelines and judgment of the investigator Further inclusion criteria apply.

Exclusion criteria:

1. Treatment with an mineralocorticoid receptor antagonist (MRA) (e.g. spironolactone,eplerenone, finerenone) within 14 days prior to Visit 1 or requiring such treatmentbefore randomisation or planned during the trial based on the judgment of theinvestigator. Treatment with MRA should not be interrupted with the intention ofenrolment into the study

2. Treatment with amiloride, or other potassium-sparing diuretic within 14 days priorto Visit 1 or requiring such treatment before randomisation or planned during thetrial based on the judgment of the investigator

3. Receiving the following treatments:

• a direct renin inhibitor (e.g. aliskiren) at Visit 2

• more than one angiotensin-converting enzyme inhibitor (ACEI), angiotensinreceptor blocker (ARB) or angiotensin receptor-neprilysin inhibitor (ARNI) usedsimultaneously at Visit 2

• In case of acute decompensated HF:

• i.v. inotrope, i.v. vasodilating drug (e.g. nitrate, nitroprusside), ori.v. natriuretic peptide (e.g. nesiritide, carperitide), or mechanicalsupport (e.g. intra-aortic balloon pump, endotracheal intubation,mechanical ventilation, any ventricular assist device) within 24 hoursprior to randomisation (Visit 2)

• i.v. diuretic with a dose that has been increased/intensified within 6hours prior to randomisation (a stable dose of an i.v. diuretic is notexclusionary)

• Systemic mineralocorticoid replacement therapy (e.g. fludrocortisone) at Visit 2

• Other aldosterone synthase inhibitors, e.g. baxdrostat at Visit 2 or plannedduring the trial

4. Myocardial infarction (MI), transient ischemic attack (TIA), stroke, coronary arterybypass graft (CABG) surgery, heart valve surgery/intervention or any other majorsurgery (major according to the investigator's assessment) within 90 days prior toVisit 2, or scheduled for major elective surgery (e.g. hip replacement, coronaryartery bypass graft surgery/CABG)

5. Percutaneous coronary intervention (PCI) ( scheduled or unscheduled) or anyangiography using iodinated contrast agents in the 7 days prior to Visit 2

6. Heart transplant recipient, awaiting heart transplant, or currently implanted leftventricular assist device (LVAD)

7. Known cardiomyopathy based on infiltrative diseases (e.g. amyloidosis), accumulationdiseases (e.g. haemochromatosis, Fabry disease), muscular dystrophies, hypertrophicobstructive cardiomyopathy or genetic hypertrophic cardiomyopathy,known pericardialconstriction, or cardiomyopathy with potentially reversible cause such as stress orperipartum cardiomyopathy or cardiomyopathy induced by chemotherapy within the 12months prior to Visit 1 and until Visit 2

8. Acute inflammatory heart disease, such as acute myocarditis, within the 90 dayspreceding prior to Visit 1 and until Visit 2

9. Known severe valvular heart disease (obstructive or regurgitant), as perinvestigator's judgment, or valvular heart disease scheduled for surgical orinvasive procedures at Visit 1, or anticipated invasive treatment during the studyFurther exclusion criteria apply.