Clinical trial • Phase III • Cardiology

EMPAGLIFLOZIN for Acute decompensated heart failure

Phase III trial of EMPAGLIFLOZIN for Acute decompensated heart failure.

Overview

Trial Therapeutic Area
Cardiology
Trial Disease
Acute decompensated heart failure
Trial Stage
Phase III
Drug Modality
Small molecule

Key dates

Initial CTIS Submission Date
13-06-2025
First CTIS Authorization Date
20-08-2025

Trial design

Randomised, open-label, control arm: matching placebo tablet, matching film-coated tablets for oral use, administered once a day orally during the in-hospital stay or until day 30. active arm: empagliflozin 10 mg once daily orally during the in-hospital stay or until day 30; after discharge (from day 31 to day 90) all participants receive open-label empagliflozin 10 mg daily. Phase III trial across 11 sites in Germany.

Randomised
Yes
Open Label
Yes
Comparator
Control arm: matching placebo tablet, matching film-coated tablets for oral use, administered once a day orally during the in-hospital stay or until day 30. Active arm: empagliflozin 10 mg once daily orally during the in-hospital stay or until day 30; after discharge (from day 31 to day 90) all participants receive open-label empagliflozin 10 mg daily.
Target Sample Size
556
Trial Duration For Participant
90

Eligibility

Recruits 556 Vulnerable populations not selected. Inclusion requires: "Written informed consent obtained". Exclusion: "Incapacity to understand and / or to provide written informed consent". Participants must be age ≥ 18 years..

Pregnancy Exclusion
Pregnancy, breastfeeding
Vulnerable Population
Vulnerable populations not selected. Inclusion requires: "Written informed consent obtained". Exclusion: "Incapacity to understand and / or to provide written informed consent". Participants must be age ≥ 18 years.

Inclusion criteria

  • {"criterion_text":"- Patients (age ≥ 18 years) with acute decompensated heart failure (HF) according to clinical assessment on active therapy with a SGLT2 inhibitor"}
  • {"criterion_text":"- Brain Natriuretic Peptide (BNP) >100 pg/ml or N-terminal pro-BNP (NT-proBNP) >300 pg/ml"}
  • {"criterion_text":"- Written informed consent obtained"}
  • {"criterion_text":"- Negative pregnancy test for women of childbearing potential"}

Exclusion criteria

  • {"criterion_text":"- Type 1 diabetes mellitus"}
  • {"criterion_text":"- Identification of any causes of heart failure leading to decompensation that needs urgent management (like acute coronary syndrome, severe unstable arrhythmias, mechanical causes, acute pulmonary embolism)"}
  • {"criterion_text":"- Incapacity to understand and / or to provide written informed consent"}
  • {"criterion_text":"- Obvious uncontrolled substance abuse"}
  • {"criterion_text":"- Pregnancy, breastfeeding"}
  • {"criterion_text":"- Chronic Kidney Disease (CKD) with eGFR<20 ml/min, or end-stage renal failure with the need for chronic dialysis treatment"}
  • {"criterion_text":"- Acute kidney injury (AKI) requiring dialysis treatment"}
  • {"criterion_text":"- Known intolerance to empagliflozin"}
  • {"criterion_text":"- Acute heart failure without signs of congestion (“dry” patient)"}
  • {"criterion_text":"- Indication for coronary angiography or any foreseeable administration of a contrast media"}
  • {"criterion_text":"- Need for hemofiltration or any other form of extracorporeal therapy"}
  • {"criterion_text":"- Planned surgery"}
  • {"criterion_text":"- Previous participation in this trial or recent participation in another clinical trial (within the last 4 weeks before inclusion)"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- The study uses a four-step hierarchical composite primary endpoint: 1) time to all-cause death (day 90) 2) number of heart failure events per patient (day 90) 3) time to first heart failure event (day 90) 4) eGFR decrease from baseline to day 90 (with a between-patient threshold defined as ≥5 ml/min/1.73 m²)","definition_or_measurement_approach":"Four-step hierarchical composite assessed at day 90 consisting of: 1) time to all-cause death (day 90); 2) number of heart failure events per patient (day 90); 3) time to first heart failure event (day 90); 4) eGFR decrease from baseline to day 90 with a between-patient threshold defined as ≥5 ml/min/1.73 m²."}

Secondary endpoints

  • {"endpoint_text":"- Cardiovascular and total mortality on day 90","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Number of patients alive and without re-hospitalization on day 90","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Re-hospitalization after initial discharge, including reason (time to first re-hospitalization after discharge, numbers of re-hospitalizations)","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Number of patients with a decrease in eGFR of 5 ml/min/1.73 m² or more from baseline to day 90","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Daily and cumulative urine output (UOP) measured from day 1 to day 6","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Diuretic efficiency (ml urine per mg furosemide equivalent) from day 1 to day 6","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Change in body weight from baseline to day 1, day 3, day 6, discharge, day 30, and day 90","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Renal function at baseline, day 3, day 6, day 30, and day 90 : •Decrease in eGFR of >20 ml/min/1.73 m2 •Doubling of serum creatinine •Need for renal replacement therapy •Total urinary sodium excretion and fractional excretion of sodium","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Liver function (bilirubin, serum aminotransferases, relevant change in coagulation status) at baseline, day 3, day 6, day 30, and day 90","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Change in NT-proBNP (alternatively calculated from BNP) from baseline to day 6, day 30, and day 90","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Quality of life (EQ-5D-3L questionnaire) on day 0, at hospital discharge, and on day 30","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Severity of HF (KCCQ-12 questionnaire) on day 0, at hospital discharge, and on day 30","definition_or_measurement_approach":""}
  • {"endpoint_text":"- IMC / ICU and hospital length of stay","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Single parameters of primary endpoint","definition_or_measurement_approach":""}

Recruitment

Planned Sample Size
556
Recruitment Window Months
21
Consent Approach
Written informed consent obtained from each participant (inclusion criterion: "Written informed consent obtained"). Participants must be ≥ 18 years. Exclusion includes: "Incapacity to understand and / or to provide written informed consent". Subject information and informed consent form documents are referenced (e.g. L1_SIS and ICF).

Geography

Total Number Of Sites
11
Total Number Of Participants
556

Germany

Earliest CTIS Part Ii Submission Date
28-07-2025
Latest Decision Or Authorization Date
22-04-2026
Processing Time Days
268
Number Of Sites
11
Number Of Participants
556

Sites

Site Name
Universitaetsklinikum Jena KöR
Department Name
Klinik für Innere Medizin I
Principal Investigator Name
Julian Westphal
Principal Investigator Email
Julian.Westphal@med.uni-jena.de
Contact Person Name
Julian Westphal
Site Name
Otto Von Guericke Universitaet Magdeburg
Department Name
Universitätsklinik für Kardiologie und Angiologie (KKAR)
Principal Investigator Name
Mariam Janashia
Principal Investigator Email
mariam.janashia@med.ovgu.de
Contact Person Name
Mariam Janashia
Contact Person Email
mariam.janashia@med.ovgu.de
Site Name
Universitaetsmedizin Goettingen
Department Name
Metabolische Kardiologie
Principal Investigator Name
Stephan von Haehling
Principal Investigator Email
stephan.von.haehling@med.uni-goettingen.de
Contact Person Name
Stephan von Haehling
Site Name
Universitätsklinikum Bonn
Department Name
Medizinische Klinik und Poliklinik II
Principal Investigator Name
Georg Nickenig
Principal Investigator Email
georg.nickenig@ukbonn.de
Contact Person Name
Georg Nickenig
Contact Person Email
georg.nickenig@ukbonn.de
Site Name
LMU Klinikum Muenchen AöR
Department Name
Medizinische Klinik und Poliklinik I
Principal Investigator Name
Stefan Kääb
Principal Investigator Email
stefan.kaab@med.uni-muenchen.de
Contact Person Name
Stefan Kääb
Site Name
Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz KöR
Department Name
Zentrum für Kardiologie
Principal Investigator Name
Moritz Brandt
Principal Investigator Email
moritz.brandt@unimedizin-mainz.de
Contact Person Name
Moritz Brandt
Site Name
Herzzentrum Dresden GmbH Universitaetsklinik
Department Name
Klinik für Innere Medizin und Kardiologie
Principal Investigator Name
Ephraim Winzer
Principal Investigator Email
ephraim.winzer@tu-dresden.de
Contact Person Name
Ephraim Winzer
Contact Person Email
ephraim.winzer@tu-dresden.de
Site Name
Universitaetsklinikum Leipzig AöR
Department Name
Klinik und Poliklinik für Kardiologie
Principal Investigator Name
Rolf Wachter
Principal Investigator Email
rolf.wachter@medizin.uni-leipzig.de
Contact Person Name
Rolf Wachter
Site Name
Rostock University Medical Center
Department Name
Klinik und Poliklinik für Kardiologie
Principal Investigator Name
Hüseyin Ince
Principal Investigator Email
hueseyin.ince@med.uni-rostock.de
Contact Person Name
Hüseyin Ince
Site Name
Kerckhoff-Klinik GmbH
Department Name
Kardiologie
Principal Investigator Name
Andreas Rieth
Principal Investigator Email
a.rieth@kerckhoff-klinik.de
Contact Person Name
Andreas Rieth
Contact Person Email
a.rieth@kerckhoff-klinik.de
Site Name
Herzzentrum Leipzig GmbH
Department Name
Kardiologie
Principal Investigator Name
Holger Thiele
Principal Investigator Email
Holger.Thiele@helios-gesundheit.de
Contact Person Name
Holger Thiele

Sponsor

Primary sponsor

Full Name
Friedrich-Schiller-Universitaet Jena
Organisation Type
Educational Institution
Country Of Registered Address
Germany

Third parties

  • {"country":"Germany","full_name":"Universitaetsklinikum Jena KöR","duties_or_roles":"[1,10,11,12,5,6,8,9]","organisation_type":"Hospital/Clinic/Other health care facility"}
  • {"country":"Germany","full_name":"Boehringer Ingelheim International GmbH, Binger Straße 173, 55216 Ingelheim am Rhein, Germany","duties_or_roles":"Monetary support","organisation_type":""}

Investigational products

Investigational Product Name
Jardiance 10 mg film-coated tablets
Active Substance
EMPAGLIFLOZIN
Modality
Small molecule
Routes Of Administration
ORAL
Route
Oral
Authorisation Status
Marketing authorisation present (EU/1/14/930/018)
Starting Dose
10 mg
Dose Levels
10 mg
Frequency
Once daily
Maximum Dose
10 mg daily
Investigational Product Name
Placebo tablet, matching film-coated tablets for oral use
Modality
Other
Routes Of Administration
ORAL
Route
Oral
Frequency
Once daily

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