Empagliflozin and Dapagliflozin in Patients Hospitalized for Acute Decompensated Heart Failure

Acute Decompensated Heart Failure Clinical Trial

— EMPATHY  

Official title:

Empagliflozin and Dapagliflozin in Patients Hospitalized for Acute Decompensated Heart Failure (EMPATHY) - a Phase III Trial.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05776043
• Other study ID #: EMPATHY
• Secondary ID: 2020-003497-4820
• Status: Recruiting
• Phase: Phase 3
• Start date: March 15, 2022
• Est. completion date: December 31, 2025

Study information

• Verified date: March 2023
• Source: Medical University of Warsaw
• Contact: Prof. Marek Postula, MD PhD
• Phone: 0048 22 1166160
• Email: mpostula[@]wum.edu.pl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

National, multicenter, randomized, double-blind, parallel-group, stratified by SGLT-2 inhibitor type, placebo-controlled trial, - a Phase III study. Primary objective of the study is to investigate the impact of SGLT-2 inhibitors (Empagliflozin and Dapagliflozin) on clinical endpoints in patients hospitalized with acute/decompensated HF.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1364
• Est. completion date: December 31, 2025
• Est. primary completion date: September 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

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 pH<7.32

• >1 episode of severe hypoglycaemia within the last 6 months under treatment with insulin or sulfonylurea

• Acute symptomatic urinary tract infection or genital infection

Related Conditions & MeSH terms

• Acute Decompensated Heart Failure
• Heart Failure

Intervention

Drug:
• Empagliflozin 10 MG
once daily for 6 or 9 months
• Dapagliflozin 10 MG
once daily for 6 or 9 months
• Placebo
once daily for 3 months

Locations

Country	Name	City	State
Poland	Autonomous Public Specialist Western John Paul II Hospital	Grodzisk Mazowiecki

Sponsors (15)

Lead Sponsor

Collaborator

Medical University of Warsaw

Autonomous Public Specialist Western John Paul II Hospital in Grodzisk Mazowiecki, Jerzy Popieluszko Bielanski Hospital in Warsaw, John Paul II Specialist Hospital in Kraków, Ludwik Rydygier Regional Polyclinical Hospital in Torun, Medical University of Gdansk, Medical University of Graz, Medical University of Silesia in Katowice, Medical University of Vienna, Nicolaus Copernicus University in Torun, Collegium Medicum in Bydgoszcz, Poznan University of Medical Sciences, Regional Polyclinical Hospital in Kielce, University Clinical Center of the Medical University of Warsaw, University Clinical Hospital Military Medical Academy, Central Veterans Hospital in Lódz, University Teaching Hospital in Bialystok

Country where clinical trial is conducted

Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to first event of adjudicated cardiovascular (CV) death, or adjudicated hospitalization for heart failure in patients with heart failure with reduced ejection fraction (HFrEF)	combined endpoint	at 3 and 9 months
Secondary	Difference in the number of recurrent hospitalizations due to heart failure between the treatment groups	recurrent hospitalizations due to heart failure	at 3 and 9 months
Secondary	Difference in the number of hospitalizations for CV causes between the treatment groups	hospitalizations for CV causes	at 3 and 9 months
Secondary	Difference in the number of hospitalizations for other than CV causes between the treatment groups	hospitalizations for other than CV causes	at 3 and 9 months
Secondary	Time to adjudicated CV death	CV death	at 3 and 9 months
Secondary	Time to adjudicated all cause death	all cause death	at 3 and 9 months
Secondary	Time to adjudicated myocardial infarction	myocardial infarction	at 3 and 9 months
Secondary	eGFR (Estimated Glomerular Filtration Rate) (CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration Equation)) creatine slope of change from baseline between the treatment groups	eGFR	at 3 and 9 months
Secondary	Difference in the number of hospital re-admissions due to heart failure between the treatment groups	hospital re-admissions due to heart failure	at 3 and 9 months
Secondary	Difference in the number of hospital re-admissions for any cause between the treatment groups	hospital re-admissions for any cause	at 3 and 9 months
Secondary	Difference in the duration of hospital stay between the treatment groups after initiation of the study treatment	duration of hospital stay	at 3 and 9 months
Secondary	Difference in the number of incidences of new onset AF and re-occurrence of AF between treatment groups	new onset AF	at 3 and 9 months
Secondary	Difference in the change of ejection fraction in echocardiography between treatment groups	ejection fraction	at 3 and 9 months
Secondary	Difference in the change of left ventricular diastolic function in echocardiography	left ventricular diastolic function	at 3 and 9 months
Secondary	Difference in the change of LV strain analysis in echocardiography	LV strain	at 3 and 9 months
Secondary	The time-averaged proportional change in NT-proBNP from	NT-proBNP	at 3 and 9 months
Secondary	The time-averaged proportional change in selected miRNA expression linked to hypertrophy, inflammation, fibrosis, apoptosis, electric stability between treatment groups and placebo group	miRNA expression	at 3 and 9 months
Secondary	The time-averaged proportional change in pre-specified biomarkers	biomarkers	at 3 and 9 months
Secondary	Change from baseline in clinical summary score (HF (Chronic Heart Failure) symptoms and physical limitations domains) of the Kansas City Cardiomyopathy Questionnaire (KCCQ)	HF score	at 3 and 9 months