EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Reduced Ejection Fraction (EMPEROR-Reduced)
Condition: Heart Failure
MeSH terms: Heart Failure
Intervention: Empagliflozin; Placebo
Intervention description: once daily; once daily
Intervention MeSH terms: Empagliflozin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 3730.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The aim of the study is to investigate the safety and efficacy of empagliflozin versus
      placebo on top of guideline-directed medical therapy in patients with heart failure with
      reduced ejection fraction.
    

Eligibility criteria:

        Inclusion criteria:

          -  Male or female patient age >= 18 years at screening. For Japan only: Age >= 20 years
             at screening

          -  Patients with chronic HF (Chronic Heart Failure) NYHA (New York Heart Association
             Classification) class II-IV and reduced EF (Ejection Fraction) (LVEF (Left Ventricular
             Ejection Fraction) <=40%) and elevated NT-proBNP (N-terminal of the prohormone brain
             natriuretic peptide)

               -  If EF >= 36% to <= 40%: NT-proBNP >= 2500 pg/ml or patients without AF (atrial
                  fibrillation/atrial flutter) and NT-proBNP >= 5000 pg/ml for patients with AF

               -  If EF >= 31% to <= 35%: NT-proBNP >= 1000 pg/ml for patients without AF and
                  NT-proBNP >=2000 pg/ml for patients with AF

               -  If EF<= 30%: NT-proBNP >= 600 pg/ml for patients without AF and NT-proBNP >=1200
                  pg/ml for patients with AF

               -  EF ≤ 40% and hospitalization for heart failure in the past 12 months: NTproBNP ≥
                  600 pg/ml for patients without AF and NT-proBNP >= 1200 pg/ml for patients with
                  AF

          -  Appropriate dose of medical therapy for HF consistent with prevailing local and
             international CV (Cardiovascular) guidelines, stable for at least 1 week prior to
             Visit 1

          -  Appropriate use of medical devices such as cardioverter defibrillator (ICD) or a
             cardiac resynchronization therapy (CRT) consistent with prevailing local or
             international CV guidelines

          -  Signed and dated written ICF (Informed Consent Form)

          -  Further inclusion criteria apply

        Exclusion criteria:

          -  Myocardial infarction, coronary artery bypass graft surgery, or other major
             cardiovascular surgery, stroke or TIA (Transient Ischaemic Attack) in past 90 days
             prior to Visit 1

          -  Heart transplant recipient, or listed for heart transplant

          -  Acute decompensated HF

          -  Systolic blood pressure (SBP) >= 180 mmHg at Visit 2.

          -  Symptomatic hypotension and/or a SBP < 100 mmHg

          -  Indication of liver disease

          -  Impaired renal function, defined as eGFR (Estimated Glomerular Filtration Rate) < 20
             mL/min/1.73 m2 (CKD-EPI (Chronic Kidney Disease - Epidemiology Collaboration
             Equation)) or requiring dialysis

          -  History of ketoacidosis

          -  Current use or prior use of a SGLT (Sodium-glucose co-transporter)-2 inhibitor or
             combined SGLT-1 and 2 inhibitor

          -  Currently enrolled in another investigational device or drug study

          -  Known allergy or hypersensitivity to empagliflozin or other SGLT-2 inhibitors

          -  Women who are pregnant, nursing, or who plan to become pregnant while in the trial

          -  Further exclusion criteria apply