This Study Tests Empagliflozin in Patients With Chronic Heart Failure With Reduced Ejection Fraction (HFrEF). The Study Looks at How Far Patients Can Walk in 6 Minutes and at Their Heart Failure Symptoms

Inclusion Criteria:

• Of full age of consent (according to local legislation, usually ≥ 18 years) atscreening.
• Male or female patients. Women of childbearing potential (WOCBP)1 must be ready andable to use highly effective methods of birth control per ICH M3 (R2) that result in alow failure rate of less than 1% per year when used consistently and correctly. A listof contraception methods meeting these criteria is provided in the patientinformation.
• Signed and dated written informed consent in accordance with ICHGCP and locallegislation prior to admission to the trial
• 6MWT distance ≤350 m at screening and at baseline.
• Patients with chronic HF diagnosed for at least 3 months before Visit 1 and currentlyin NYHA class II-IV
• Chronic HF with reduced EF defined as LVEF ≤ 40 % as per echocardiography at Visit 1as per local reading (obtained under stable condition).
• Elevated NT-proBNP > 450 pg/ml for patients without atrial fibrillation (AF) ORNTproBNP > 600 pg/ml for patients with AF as analysed at the Central laboratory atVisit 1
• Patients must be clinically stable and on appropriate and stable dose of medicaltherapy for HF (such as ACEi, ARB, β-blocker, oral diuretics, MRA, ARNI, ivabradine),consistent with prevailing CV guidelines, stable for at least 4 weeks prior to Visit 1(screening) with the exception of diuretics which must have been stable for at leasttwo weeks prior to Visit 1. The investigator must document the reason in case thepatient is not on such medication or if not on target dose of any heart failuremedication as per local guidelines.
• Clinically stable at randomization with no signs of heart failure decompensation (asper investigator judgement).
• Appropriate use of medical devices such as cardioverter defibrillator (ICD) or acardiac resynchronization therapy (CRT) consistent with prevailing local orinternational CV guidelines, and if a device is required, it must have been implantedfor at least 3 months prior to visit 1 for CRT and 1 month prior to visit 1 for ICD.

Exclusion Criteria:

• Myocardial infarction (increase in cardiac enzymes in combination with symptoms ofischaemia or newly developed ischaemic ECG changes), coronary artery bypass graftsurgery or other major cardiovascular surgery, stroke or TIA in past 90 days prior toVisit 1
• Acute decompensated HF (exacerbation of chronic HF) requiring intravenous (i.v.)diuretics, i.v. inotropes or i.v. vasodilators, or left ventricular assist devicewithin 4 weeks prior to Visit 1, and/or during screening period until Visit 2
• Previous or current randomisation in another Empagliflozin Heart Failure trial (i.e.studies 1245.110, 1245.121, 1245-0167)
• Type 1 Diabetes Mellitus (T1DM)
• Impaired renal function, defined as eGFR < 20 mL/min/1.73 m2 (CKD-EPIcr) or requiringdialysis, as determined at Visit 1
• Symptomatic hypotension or a SBP < 100 mmHg at Visit 1 or 2
• Systolic blood pressure (SBP) ≥ 180 mmHg at Visit 1 or 2, or SBP >160mmHg at bothVisit 1 and 2
• Atrial fibrillation or atrial flutter with a resting heart rate >110 bpm documented byECG at Visit 1 (Screening)
• Unstable angina pectoris in past 30 days prior to Visit 1
• Largest distance walked in 6 minutes (6MWTD) at baseline <100m.
• Any presence of condition that precludes exercise testing such as:
• claudication,
• uncontrolled (according to investigator judgement) bradyarrhythmia ortachyarrhythmia,
• significant musculoskeletal disease,
• primary pulmonary hypertension,
• severe obesity (body mass index ≥40.0 kg/m2),
• orthopedic conditions that limit the ability to walk (such as arthritis in theleg, knee or hip injuries)
• amputation with artificial limb without stable prosthesis function for the past 3months
• Any condition that, in the opinion of the investigator, would contraindicate theassessment of 6MWT
• Patients in a structured (according to Investigator judgement) exercise trainingprogram in the 1 month prior to screening or planned to start one during the course ofthis trial.
• Planned implantation of ICD or CRT during the course of the trial.
• Treatment with i.v. iron therapy or erythropoietin within 3 months prior to screening
• Treatment with i.v. iron therapy or erythropoietin within 3 months prior to screening
• Further exclusion criteria applies