This Study Tests Empagliflozin in Patients With Chronic Heart Failure With Preserved Ejection Fraction (HFpEF). 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: 315.0
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 (6MWT) in patients with chronic
      heart failure (CHF) with preserved 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 child bearing potential (WOCBP) 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

          -  Six minute walk test (6MWT) distance ≤350 m at screening and at baseline.

          -  Patients with CHF diagnosed for at least 3 months before Visit 1, and currently in
             NYHA class II-IV

          -  Chronic heart failure (CHF) with preserved Ejection fraction (EF) defined as left
             ventricle ejection fraction(LVEF) > 40 % as per echocardiography at Visit 1 per local
             reading and no prior measurement of LVEF ≤ 40% under stable conditions.

          -  Elevated N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) > 300 pg/ml for patients
             without atrial fibrillation (AF), OR > 600 pg/ml for patients with AF, as analysed at
             the Central laboratory at Visit 1

          -  Patients must have at least one of the following evidence of heart failure (HF):

               -  Structural heart disease (left atrial enlargement and/or left ventricular
                  hypertrophy) documented by echocardiogram at Visit 1, OR

               -  Documented Hospitalization for Heart Failure (HHF) within 12 months prior to
                  Visit 1

          -  Consistent with prevailing CV guidelines, if oral diuretics are prescribed to control
             symptoms, patients must be on an appropriate and stable dose of oral diuretics for at
             least 2 weeks prior to Visit 1 to control symptoms.

          -  Clinically stable at randomization with no signs of heart failure decompensation (as
             per investigator judgement).

        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 transient ischemic attack in
             past 90 days prior to Visit 1

          -  Acute decompensated HF (exacerbation of CHF) 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, 1245-0168)

          -  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 systolic blood pressure (SBP) < 100 mmHg at Visit 1 or 2

          -  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.

          -  ICD implantation within 1 month prior to Visit 1 or planned during the course of the
             trial

          -  Implanted cardiac resynchronisation therapy (CRT)

          -  Treatment with i.v. iron therapy or erythropoietin (EPO) within 3 months prior to
             screening.

          -  Further exclusion criteria applies