Effects of Empagliflozin on Diuresis and Renal Function in Patients With Acute Decompensated Heart Failure
Condition: Acute Decompensated Heart Failure
MeSH terms: Heart Failure
Study type: Interventional
Phase: Phase 2

Summary: 
      Heart failure is the most common hospital admission diagnosis and shows increasing incidence
      and prevalence in Germany, the United States and worldwide. Improvements in the primary
      treatment conditions for e.g. myocardial infarction and reduced primary mortality has
      resulted in an increasing group of patients with secondary cardiac abnormalities including
      chronic heart failure.

      Progressive cardiac dysfunction and failure are associated with exercise intolerance, volume
      retention, nocturia, dyspnoea among others. The most severe progression of heart failure is
      cardiac decompensation (also called: acute heart failure) and cardiogenic shock. Volume
      retention, abnormal renal function and diuretic resistance are hallmarks of this clinical
      phenotype. Currently, the only available treatment is diuresis through various combinations
      of diuretics and the addition of cardiac inotropes when cardiac hypoperfusion is documented.
      Patients with acute decompensated heart failure (ADHF) often develop a state of diuretic
      resistance characterized by a need of rising dosages of diuretics for adequate diuresis and
      urine production.

      ADHF patients also show metabolic abnormalities including insulin resistance or type 2
      diabetes mellitus.

      Empagliflozin is a potent and selective inhibitor of the sodium glucose cotransporter 2
      (SGLT2) used in the treatment of type 2 diabetes. By inhibiting SGLT2, empagliflozin reduces
      renal glucose reabsorption and increases urinary glucose excretion. In addition to reducing
      hyperglycaemia, empagliflozin is associated with osmotic diuresis, reductions in weight and
      blood pressure without increases in heart rate, and has favourable effects on markers of
      arterial stiffness and vascular resistance.

      The investigators propose a single center exploratory study to test the hypothesis that the
      application of empagliflozin in addition to standard diuretic regimens increases urine
      output, decreases the need for further acceleration of diuretic regimens, and positively
      influences renal function as well as metabolism including insulin resistance in ADHF
      patients. Thereby, empagliflozin may be effective in the prevention of complex cardio
      metabolic alterations involved in ADHF.
    

Detailed description: 
      If feasible (run-in of patients into the hospital from 08:00 a.m. to 06:00 p.m.)
      screening/baseline, enrolment, randomization and first dose of empagliflozin should be
      performed on the same day. In general, but especially in case of other run-in times (e.g.
      late evening, night and early morning hours) screening/baseline time period should not exceed
      12 hours. In case a patient has to spend the night in hospital before randomization can be
      executed, a time period of up to 16 hours will not be counted as protocol deviation.
    

Intervention name(s): Empagliflozin 25 mg; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Empagliflozin 25 mg film-coated tablets, for oral use administered once daily for 5 days in addition to routinely administered (weight adjusted) intravenous furosemide; matching Placebo, film-coated tablets, for oral use, matching to investigational product Jardiance® administered once daily for 5 days in addition to routinely administered (weight adjusted) intravenous furosemide
Intervention MeSH terms: Empagliflozin
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Single-center, prospective, double-blind, placebo-controlled, randomized and interventional exploratory study
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: acute decompensated heart failure; empagliflozin; diuresis; renal function