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
Condition: Heart Failure
MeSH terms: Heart Failure
Intervention: Empagliflozin; Placebo
Intervention description: Film-coated tablet; Film-coated tablet
Intervention MeSH terms: Empagliflozin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 312.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The primary objective of the study is to evaluate the effect of empagliflozin 10 mg versus
      placebo on exercise ability using the 6 minute walk test in patients with chronic HF with
      reduced ejection fraction (LVEF ≤ 40%) Secondary objectives are to assess Patient-Reported
      Outcome (PRO)
    

Eligibility criteria:

        Inclusion Criteria:

          -  Of full age of consent (according to local legislation, usually ≥ 18 years) at
             screening.

          -  Male or female patients. Women of childbearing potential (WOCBP)1 must be ready and
             able to use highly effective methods of birth control per ICH M3 (R2) that result in a
             low failure rate of less than 1% per year when used consistently and correctly. A list
             of contraception methods meeting these criteria is provided in the patient
             information.

          -  Signed and dated written informed consent in accordance with ICHGCP and local
             legislation 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 currently
             in NYHA class II-IV

          -  Chronic HF with reduced EF defined as LVEF ≤ 40 % as per echocardiography at Visit 1
             as per local reading (obtained under stable condition).

          -  Elevated NT-proBNP > 450 pg/ml for patients without atrial fibrillation (AF) OR
             NTproBNP > 600 pg/ml for patients with AF as analysed at the Central laboratory at
             Visit 1

          -  Patients must be clinically stable and on appropriate and stable dose of medical
             therapy 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 least
             two weeks prior to Visit 1. The investigator must document the reason in case the
             patient is not on such medication or if not on target dose of any heart failure
             medication as per local guidelines.

          -  Clinically stable at randomization with no signs of heart failure decompensation (as
             per investigator judgement).

          -  Appropriate use of medical devices such as cardioverter defibrillator (ICD) or a
             cardiac resynchronization therapy (CRT) consistent with prevailing local or
             international CV guidelines, and if a device is required, it must have been implanted
             for 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 of
             ischaemia or newly developed ischaemic ECG changes), coronary artery bypass graft
             surgery or other major cardiovascular surgery, stroke or TIA in past 90 days prior to
             Visit 1

          -  Acute decompensated HF (exacerbation of chronic HF) requiring intravenous (i.v.)
             diuretics, i.v. inotropes or i.v. vasodilators, or left ventricular assist device
             within 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 requiring
             dialysis, 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 both
             Visit 1 and 2

          -  Atrial fibrillation or atrial flutter with a resting heart rate >110 bpm documented by
             ECG 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 or
                  tachyarrhythmia,

               -  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 the
                  leg, knee or hip injuries)

               -  amputation with artificial limb without stable prosthesis function for the past 3
                  months

               -  Any condition that, in the opinion of the investigator, would contraindicate the
                  assessment of 6MWT

          -  Patients in a structured (according to Investigator judgement) exercise training
             program in the 1 month prior to screening or planned to start one during the course of
             this 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