Empagliflozin and Dapagliflozin in Patients Hospitalized for Acute Decompensated Heart Failure (EMPATHY)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Acute Decompensated Heart Failure
• Intervention / Treatment: Drug: Empagliflozin 10 MG; Drug: Dapagliflozin 10 MG; Drug: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 1364
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Prof. Marek Postula, MD PhD; Phone Number: 0048 22 1166160; Email: mpostula@wum.edu.pl
• Study Contact Backup: Name: Prof. Jolanta M. Siller-Matula, MD PhD; Email: Jolanta.Siller-Matula@meduniwien.ac.at

Study Locations

• Poland
  • Grodzisk Mazowiecki, Poland
    • Recruiting
    • Autonomous Public Specialist Western John Paul II Hospital
    • Contact: Janusz Bednarski

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: SGLT 2 Inhibitor; Empagliflozin (n=341) or Dapagliflozin (n=341): 9 months of treatment	Drug: Empagliflozin 10 MG; once daily for 6 or 9 months; Other Names: Jardiance; Drug: Dapagliflozin 10 MG; once daily for 6 or 9 months; Other Names: Forxiga
Placebo Comparator: Placebo with a switch to SGLT 2 Inhibitor; Placebo (n=682) for 3 months of treatment with a subsequent switch to Empagliflozin (n=341) or Dapagliflozin (n=341): 6 months of treatment	Drug: Placebo; once daily for 3 months; Other Names: Placebo with switch to SGLT2 inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Difference in the number of hospitalizations for CV causes between the treatment groups	hospitalizations for CV causes	at 3 and 9 months
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
Time to adjudicated CV death	CV death	at 3 and 9 months
Time to adjudicated all cause death	all cause death	at 3 and 9 months
Time to adjudicated myocardial infarction	myocardial infarction	at 3 and 9 months
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
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
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
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
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
Difference in the change of ejection fraction in echocardiography between treatment groups	ejection fraction	at 3 and 9 months
Difference in the change of left ventricular diastolic function in echocardiography	left ventricular diastolic function	at 3 and 9 months
Difference in the change of LV strain analysis in echocardiography	LV strain	at 3 and 9 months
The time-averaged proportional change in NT-proBNP from	NT-proBNP	at 3 and 9 months
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
The time-averaged proportional change in pre-specified biomarkers	biomarkers	at 3 and 9 months
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

Collaborators and Investigators

• Sponsor: Medical University of Warsaw
• Collaborators: Medical University of Graz; Medical University of Vienna; Poznan University of Medical Sciences; Medical University of Gdansk; University Clinical Center of the Medical University of Warsaw; Jerzy Popiełuszko Bielański Hospital in Warsaw; Regional Polyclinical Hospital in Kielce; University Clinical Hospital Military Medical Academy, Central Veterans Hospital in Łódź; Autonomous Public Specialist Western John Paul II Hospital in Grodzisk Mazowiecki; Nicolaus Copernicus University in Toruń, Collegium Medicum in Bydgoszcz; John Paul II Specialist Hospital in Kraków; Ludwik Rydygier Regional Polyclinical Hospital in Toruń; University Teaching Hospital in Białystok; Medical University of Silesia in Katowice

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2022
• Primary Completion (Anticipated): September 30, 2024
• Study Completion (Anticipated): December 31, 2025

Study Registration Dates

• First Submitted: April 4, 2022
• First Submitted That Met QC Criteria: March 7, 2023
• First Posted (Actual): March 20, 2023

Study Record Updates

• Last Update Posted (Actual): March 20, 2023
• Last Update Submitted That Met QC Criteria: March 7, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: acute heart failure; dapagliflozin; decompensated heart failure; empagliflozin; SGLT-2 inhibitors
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Dapagliflozin; Empagliflozin; Sodium-Glucose Transporter 2 Inhibitors
• Other Study ID Numbers: EMPATHY; 2020-003497-48 (EudraCT Number); 2019/ABM/01/00037 (Other Grant/Funding Number: Medical Research Agency (ABM))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No