Empagliflozin and dapagliflozin for improvement of outcome in patients with acute heart failure

Empagliflozin and dapagliflozin in patients hospitalized for acute decompensated heart failure (EMPATHY) – a phase III trial - EMPATHY

Status

Active, not recruiting

Phases

Phase 3

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2020-003497-48-PL

Enrollment

1364

Registered

2021-09-08

Start date

2021-11-29

Completion date

Unknown

Last updated

2025-01-07

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

acute decompensated heart failure MedDRA version: 20.0 Level: LLT Classification code 10010684 Term: Congestive heart failure System Organ Class: 100000004849

Interventions

Trade Name: Empagliflozin/Jardiance Pharmaceutical Form: Tablet INN or Proposed INN: Empagliflozin, Jardiance CAS Number: 864070-44-0 Concentration unit: mg milligram(s) Concentration type: equal Conc

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: - Patients 18 years of age with the capacity to provide written informed consent - Currently hospitalized for a primary diagnosis of acute/decompensated HF (HFrEF, HFmrEF,HFpEF), including symptoms and signs of fluid overload regardless of ejection fraction or diabetes status - In patients with HFpEF the diagnosis has to be confirmed according to the current HFpEF definition (by non-invasive testing: evidence of structural or functional changes in the heart as evidenced on echocardiography or by invasive testing as LVEDP assessment or right heart catheterisation). - Randomized no earlier than 24 hours and up to 10 days after initial presentation while still hospitalized - Stable as defined by: systolic blood pressure (SBP>100 mmHg for the preceding 6 hours) - No intensification of IV diuretics within the last 6 hours, - No use of IV vasodilators within the last 6 hours, - No use of IV inotropes or levosimendan within the last 24 hours prior to randomization - Elevated NT-proBNP >600 pg/mL during the current hospitalization in patients with HFrEF and >300 pg/mL in patients with HFmrEF or HFpEF (or above 900 pg/ml if atrial fibrillation is present at admission independently from EF). - eGFR >20 ml/min/1,73m2 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 364 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 1000

Exclusion criteria

Exclusion criteria: - History of ketoacidosis - Type 1 diabetes - SGLT-2 Inhibitor at baseline or known allergy to SGLT-2 Inhibitors - Current active cancer with less than 2 years of life expectancy - Pulmonary embolism, cerebrovascular accident as the primary trigger for the current hospitalization - Cardiomyopathy based on infiltrative diseases (e.g. amyloidosis), accumulation diseases (e.g. haemochromatosis, Fabry disease), muscular dystrophies, cardiomyopathy with reversible causes (e.g. stress cardiomyopathy), hypertrophic obstructive cardiomyopathy or known pericardial constriction - Any severe (obstructive or regurgitant) valvular heart disease, expected to lead to surgery during the trial period - Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant - Blood pH1 episode of severe hypoglycaemia within the last 6 months under treatment with insulin or sulfonylurea - Acute symptomatic urinary tract infection or genital infection

Design outcomes

Primary

Measure	Time frame
Main Objective: 1.to investigate the impact of SGLT-2 inhibitors (Empagliflozin and Dapagliflozin) on clinical endpoints in patients with acute/decompensated HF regardless of ejection fraction (HFrEF, HFmEF, HFpEF) or diabetes status within 9 months after the event;Secondary Objective: Secondary objectives: 1. to investigate and compare the impact of SGLT-2 inhibitors on cardiac function based on echocardiography and biomarkers, including non-coding RNA (ncRNA) and microbiome metabolites in patients acute/decompensated HF 2.to evaluate the utility of specific circulating ncRNAs along with microbiome metabolites, biomarkers related with fibrosis, inflammation and cardiac remodeling processes and classic biomarkers for monitoring therapy with SGLT-2 inhibitors and its potential impact on expression of ncRNAs related to pathogenesis of acute/decompensated HF 3.to propose a risk score prediction tool for the course of acute/decompensated HF and therapy monitoring with SGLT-2 inhibitors based on concomitant usage of both selected ncRNA and biomarkers related to molecular pathways associated with disease progression. ;Primary end point(s): Composite primary endpoint - time to first event of all-cause death or worsening HF (defined as worsening signs or symptoms of HF that require an intensification of diuretic therapy or any other intravenous therapy for HF or mechanical ventilatory, renal or circulatory support) or HF readmission (unplanned ambulatory visit or hospitalization due to symptoms of HF through 3 months). ;Timepoint(s) of evaluation of this end point: Time of first event of all-cause death or worsening HF (defined as worsening signs or symptoms of HF that require an intensification of diuretic therapy or any other intravenous therapy for HF or mechanical ventilatory, renal or circulatory support) or HF readmission; (unplanned ambulatory visit or hospitalization due to symptoms of HF through 3 months).	—

Measure

Time frame

Main Objective: 1.to investigate the impact of SGLT-2 inhibitors (Empagliflozin and Dapagliflozin) on clinical endpoints in patients with acute/decompensated HF regardless of ejection fraction (HFrEF, HFmEF, HFpEF) or diabetes status within 9 months after the event;Secondary Objective: Secondary objectives: 1. to investigate and compare the impact of SGLT-2 inhibitors on cardiac function based on echocardiography and biomarkers, including non-coding RNA (ncRNA) and microbiome metabolites in patients acute/decompensated HF 2.to evaluate the utility of specific circulating ncRNAs along with microbiome metabolites, biomarkers related with fibrosis, inflammation and cardiac remodeling processes and classic biomarkers for monitoring therapy with SGLT-2 inhibitors and its potential impact on expression of ncRNAs related to pathogenesis of acute/decompensated HF 3.to propose a risk score prediction tool for the course of acute/decompensated HF and therapy monitoring with SGLT-2 inhibitors based on concomitant usage of both selected ncRNA and biomarkers related to molecular pathways associated with disease progression. ;Primary end point(s): Composite primary endpoint - time to first event of all-cause death or worsening HF (defined as worsening signs or symptoms of HF that require an intensification of diuretic therapy or any other intravenous therapy for HF or mechanical ventilatory, renal or circulatory support) or HF readmission (unplanned ambulatory visit or hospitalization due to symptoms of HF through 3 months). ;Timepoint(s) of evaluation of this end point: Time of first event of all-cause death or worsening HF (defined as worsening signs or symptoms of HF that require an intensification of diuretic therapy or any other intravenous therapy for HF or mechanical ventilatory, renal or circulatory support) or HF readmission; (unplanned ambulatory visit or hospitalization due to symptoms of HF through 3 months).

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Secondary

Measure	Time frame
Secondary end point(s): 1. Composite secondary endpoint - time to first event of all-cause death or worsening HF (defined as worsening signs or symptoms of HF that require an intensification of diuretic therapy or any other intravenous therapy for HF or mechanical ventilatory, renal or circulatory support) or HF readmission (unplanned ambulatory visit or hospitalization due to symptoms of HF through 9 months 2. Difference in the number of recurrent hospitalizations due to heart failure between the treatment groups: at 3 and 9 months.. 3. Difference in the number of hospitalizations for CV causes between the treatment groups: - time frame: at 3 and 9 months. 4. Difference in the number of hospitalizations for other than CV causes between the treatment groups: - time frame: at 3 and 9 months. 5. Time to adjudicate CV death- time frame: at 3 and 9 months. 6. Time to adjudicate all causes of death- time frame: at 3 and 9 months. 7. Time to adjudicate myocardial infarction- time frame: at 3 and 9 months. 8. eGFR (Estimated Glomerular Filtration Rate) (CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration Equation)) CR slope of change from baseline: at 3 and 9 months. 9. Difference in the number of hospital readmissions due to heart failure between the treatment groups- time frame: at 3 and 9 months. 10. Difference in the number of hospital readmissions for any cause between the treatment groups- time frame: at 3 and 9 months. 11. Difference in the duration of hospital stay between the treatment groups after initiation of the study treatment- time frame: at 3 and 9 months. 12. Difference in the number of incidences of new onset AF and re-occurrence of AF between treatment groups- time frame: at 3 and 9 months. 13. Difference in the change of ejection fraction in echocardiography between treatment groups from randomization to 3 and 9 months. 14. Difference in the change of left ventricular diastolic function in echocardiography from randomization to 3 and 9 months. 1	—

Measure

Time frame

Secondary end point(s): 1. Composite secondary endpoint - time to first event of all-cause death or worsening HF (defined as worsening signs or symptoms of HF that require an intensification of diuretic therapy or any other intravenous therapy for HF or mechanical ventilatory, renal or circulatory support) or HF readmission (unplanned ambulatory visit or hospitalization due to symptoms of HF through 9 months 2. Difference in the number of recurrent hospitalizations due to heart failure between the treatment groups: at 3 and 9 months.. 3. Difference in the number of hospitalizations for CV causes between the treatment groups: - time frame: at 3 and 9 months. 4. Difference in the number of hospitalizations for other than CV causes between the treatment groups: - time frame: at 3 and 9 months. 5. Time to adjudicate CV death- time frame: at 3 and 9 months. 6. Time to adjudicate all causes of death- time frame: at 3 and 9 months. 7. Time to adjudicate myocardial infarction- time frame: at 3 and 9 months. 8. eGFR (Estimated Glomerular Filtration Rate) (CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration Equation)) CR slope of change from baseline: at 3 and 9 months. 9. Difference in the number of hospital readmissions due to heart failure between the treatment groups- time frame: at 3 and 9 months. 10. Difference in the number of hospital readmissions for any cause between the treatment groups- time frame: at 3 and 9 months. 11. Difference in the duration of hospital stay between the treatment groups after initiation of the study treatment- time frame: at 3 and 9 months. 12. Difference in the number of incidences of new onset AF and re-occurrence of AF between treatment groups- time frame: at 3 and 9 months. 13. Difference in the change of ejection fraction in echocardiography between treatment groups from randomization to 3 and 9 months. 14. Difference in the change of left ventricular diastolic function in echocardiography from randomization to 3 and 9 months. 1

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Countries

Poland

Contacts

Public ContactCEPT

Medical University of Warsaw/Marek Postula

mpostula@wum.edu.pl+4822116 61 60

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026