SGLT2 Inhibition in Combination With Diuretics in Heart Failure
Condition: Heart Failure; Type 2 Diabetes Mellitus
MeSH terms: Heart Failure; Diabetes Mellitus; Diabetes Mellitus, Type 2
Study type: Interventional
Phase: Phase 4

Summary: 
      The RECEDE-CHF trial is a single centre phase IV, randomised, double-blind,
      placebo-controlled, crossover trial conducted in NHS Tayside, Scotland comparing
      empagliflozin 25mg, to placebo in patients with Type 2 Diabetes and mild Chronic Heart
      Failure with left ventricular systolic dysfunction who are already on a loop diuretic. Renal
      physiological testing will be performed at two points on each arm to assess the effect of
      empagliflozin, on urinary volume, compared to placebo. The secondary outcomes are to assess
      the effect of empagliflozin in addition to loop diuretics on natriuresis, to assess the
      safety of add-on SGLT2 inhibitor therapy as measured by changes to serum creatinine and eGFR,
      to assess effects of empagliflozin on urinary protein/creatinine ratio, albumin/creatinine
      ratio and cystatin C when compared to placebo.
    

Detailed description: 
      Type 2 Diabetes (T2D) and Heart Failure (HF) are a frequent combination, where treatment
      options remain limited. There has been increasing interest around the sodium-glucose
      co-transporter 2 (SGLT2) inhibitors and their use in patients with HF. This is following
      publication of EMPA-REG OUTCOME trial that reported a 14% reduction in the primary composite
      outcome of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke and >30%
      reductions in cardiovascular mortality, overall mortality and HF hospitalisations in patients
      randomised to the SGLT2 inhibitor, empagliflozin, when compared to placebo. Data on the
      effect of SGLT2 inhibitor use with diuretics is limited. We hypothesize that, in the diabetic
      CHF population, SGLT2 inhibition may augment the effects of loop diuretics.

      Renal Physiology Test (RPT) days will be performed at week 1 and week 6 on each arm of this
      crossover trial. On these RPT days participants will undergo oral water loading (15mls/kg)
      and frequent urination at 30 minute intervals to gain a steady state diuresis. The
      investigational medicinal product will be administered, followed by an intravenous bolus of
      furosemide at a dose of half the participant's usual loop diuretic dose.

      This proof of concept trial will aim to shed light on the mechanism of the cardiovascular and
      renal outcomes demonstrated in the recent EMPA-REG study by documenting the influence of the
      SGLT2 inhibitors when used in combination with a loop diuretic on diuresis and natriuresis
      when compared to placebo.

      The RECEDE-CHF trial is funded by the British Heart Foundation (BHF grant number: 807998).
      NAM is a BHF funded clinical research fellow.
    

Intervention name(s): Empagliflozin 25mg; Placebo oral capsule; Frusemide
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Empagliflozin (SGLT2 inhibitor) 25 mg once daily for 6 weeks; Capsules containing microcrystalline cellulose Ph Eur over encapsulated in a hard gelatine capsule shell to match the active comparator once daily for 6 weeks; Renal Physiology Test (RPT) days will be performed at week 1 and week 6 on each arm of this crossover trial. On these RPT days participants will undergo oral water loading (15mls/kg) and frequent urination at 30 minute intervals to gain a steady state diuresis. At a set time point, an intravenous bolus of furosemide at a dose of half the participant's usual loop diuretic dose will be administered.
Other intervention name(s): Jardiance; Placebo
Intervention MeSH terms: Empagliflozin; Furosemide
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: 6 week period of Investigational Medicinal Product (Empagliflozin 25 mg od) or placebo. A 2 week washout period will then be observed, followed by the second arm with a further 6 week period of placebo or IMP. At week 1 and week 6 of each arm, detailed Renal Physiology Test days will be performed.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Heart Failure; Type 2 Diabetes Mellitus; Sodium-Glucose co-Transporter 2 (SGLT2) inhibitors; Natriuresis; Diuresis