Analysing the Effect of Empagliflozin on Reduction of Tissue Sodium Content in Patients With Chronic Heart Failure
Condition: Chronic Heart Failure
MeSH terms: Heart Failure
Study type: Interventional
Phase: Phase 2

Summary: 
      The hypothesis is that the SGLT-2 inhibitor empagliflozin reduces tissue sodium content in
      patients with chronic heart failure, and if the hypothesis is proven, that this mechanism
      contributes to the beneficial effects found in EMPA-REG Outcome trial potentially via
      exerting beneficial effects on the vascular structure and function of the micro- and
      macrocirculation.
    

Detailed description: 
      SGLT-2 inhibitors such as empagliflozin inhibit the SGLT-2 transport in the proximal tubular
      cells of the kidney, thereby causing glucosuria to approximately 100 g per day (and sometimes
      even more). The SGLT-2 inhibition does not only cause glucosuria but also natriuresis, since
      with each molecule of glucose one molecule of sodium is inhibited to be reabsorbed. Indeed,
      during the first week SGLT-2 inhibition causes clinically detectable natriuresis but its
      effect in the long run is not yet illustrated. Of course, a new sodium balance will be
      achieved after a certain time (otherwise the human body would be completely salt depleted),
      but total sodium content could be different. With new innovative magnetic resonance imaging
      (MRI) technology we are able to assess tissue sodium content in the skin and muscle, and
      observed that sodium content is significantly increased with aging, severe hypertension or
      hyperaldosteronism. Furthermore, skin sodium content assessed by MRI was closely related to
      left ventricular mass (r=0.559, p<0.0001, N=89) independently of age, gender, body mass
      index, and 24 h ambulatory blood pressure (β=0.343, p=0.001, N=89) 11. Using this technology,
      our first yet unpublished data (clinicaltrials.gov: NCT02383238) indicate that SGLT-2
      inhibition decreases sodium content in the skin in patients with diabetes. Finally, we
      observed previously that in patients with acute chronic heart failure skin sodium content
      decreased from 43.5 mmol/l to 32.2 mmol/l after diuretic therapy.

      Thus, the present study aims at analyzing changes in total and tissue sodium content after
      SGLT-2 inhibition with empagliflozin. In parallel, sodium intake and excretion and central
      systolic and pulse pressure as well as other vascular parameters will be assessed. In face of
      the upcoming studies with empagliflozin conducted in patients with reduced and preserved
      ejection fraction (two large-scale, prospective, doubleblind, placebo controlled studies
      planned by Boehringer Ingelheim as the sponsor), we thought that we focus on patients with
      chronic heart failure irrespective diabetic status. The hypothesis is that the SGLT-2
      inhibitor empagliflozin reduces tissue sodium content in patients with chronic heart failure,
      and if the hypothesis is proven, that this mechanism contributes to the beneficial effects
      found in EMPA-REG Outcome trial potentially via exerting beneficial effects on the vascular
      structure and function of the micro- and macrocirculation.
    

Intervention name(s): Empagliflozin 10mg; Placebo Oral Tablet
Intervention type(s): Drug; Drug
Intervention description(s): Each patient, after the run-in/wash-out phase, will be randomly assigned in a doubleblind fashion to one of the two treatment sequences according to a randomisation list.
and provided by the sponsor.; Each patient, after the run-in/wash-out phase, will be randomly assigned in a doubleblind fashion to one of the two treatment sequences according to a randomisation list.
and provided by the sponsor.
Other intervention name(s): EMPA; PLACEBO
Intervention MeSH terms: Empagliflozin
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Phase II, randomized (2:1), prospective, double-blind, placebo controlled, parallel-group, single center study.
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: SGLT-2 inhibitor, Chronic heart failure, tissue sodium,