NCT04049045: EMPAG-HF

Effects of Empagliflozin on Diuresis and Renal Function in Patients With Acute Decompensated Heart Failure

Completed Phase 2 Last updated 3 August 2021

What this trial tests

Phase 2 trial testing Empagliflozin 25 mg in Acute Decompensated Heart Failure in 60 participants. Completed in 29 June 2021.

Timeline

29 September 2019

Primary endpoint
30 May 2021

29 June 2021

Quick facts

Lead sponsor	Christian Schulze
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	triple
Primary purpose	treatment
Enrollment	60
Start date	29 September 2019
Primary completion	30 May 2021
Estimated completion	29 June 2021
Sites	1 location across Germany

Drugs / interventions tested

• Empagliflozin 25 mg — full drug profile →
• Placebo

Conditions studied

• Acute Decompensated Heart Failure — all drugs for Acute Decompensated Heart Failure →

Sponsor

Christian Schulze

Who can join

Adults 18 to 85, any sex, with Acute Decompensated Heart Failure. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

7 peer-reviewed publications reference this trial (live from Europe PMC):

1. Effects of Early Empagliflozin Initiation on Diuresis and Kidney Function in Patients With Acute Decompensated Heart Failure (EMPAG-HF).
   Schulze PC, Bogoviku J, Westphal J, Aftanski P, et al · · 2022 · cited 144× · PMID 35766022 · DOI 10.1161/circulationaha.122.059038
2. Sodium-glucose cotransporter 2 inhibitor effects on heart failure hospitalization and cardiac function: systematic review.
   Rasalam R, Atherton JJ, Deed G, Molloy-Bland M, et al · · 2021 · cited 16× · PMID 34219407 · DOI 10.1002/ehf2.13483
3. Sodium-Glucose Co-transporter 2 Inhibitors in the Failing Heart: a Growing Potential.
   Brito D, Bettencourt P, Carvalho D, Ferreira J, et al · · 2020 · cited 16× · PMID 32350793 · DOI 10.1007/s10557-020-06973-3
4. Acute effects of empagliflozin on left atrial and ventricular filling parameters using echocardiography-a subanalysis of the EMPAG-HF trial.
   Bogoviku J, Nguyen TD, Westphal JG, Aftanski P, et al · · 2025 · cited 10× · PMID 40037298 · DOI 10.1093/ehjcvp/pvaf003
5. Early Initiation of Sodium-Glucose Cotransporter 2 Inhibitors in Acute Heart Failure: A Systematic Review and Meta-Analysis.
   Cherbi M, Lairez O, Baudry G, Gautier P, et al · · 2025 · cited 4× · PMID 40194974 · DOI 10.1161/jaha.124.039105
6. Dapagliflozin in Acute Cardiovascular Conditions: Insights From the DEFENDER Trial.
   Tavares CAM, Azevedo LCP, Guimarães PO, Rea-Neto Á, et al · · 2026 · cited 1× · PMID 41421016 · DOI 10.1016/j.jacadv.2025.102459
7. Effects of empagliflozin on uric acid levels during acute heart failure recompensation: A sub-analysis of the EMPAG-HF trial (Effects of Empagliflozin on Diuresis and Renal Function in Patients with Acute Decompensated Heart Failure).
   Bogoviku J, Nguyen TD, Westphal JG, Haertel F, et al · · 2025 · PMID 40631522 · DOI 10.1002/ejhf.3723