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

Primary Purpose

Acute Decompensated Heart Failure

Status
Recruiting
Phase
Phase 3
Locations
Poland
Study Type
Interventional
Intervention
Empagliflozin 10 MG
Dapagliflozin 10 MG
Placebo
Sponsored by
Medical University of Warsaw
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Decompensated Heart Failure focused on measuring SGLT-2 inhibitors, dapagliflozin, empagliflozin, acute heart failure, decompensated heart failure

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Autonomous Public Specialist Western John Paul II HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

SGLT 2 Inhibitor

Placebo with a switch to SGLT 2 Inhibitor

Arm Description

Empagliflozin (n=341) or Dapagliflozin (n=341): 9 months of treatment

Placebo (n=682) for 3 months of treatment with a subsequent switch to Empagliflozin (n=341) or Dapagliflozin (n=341): 6 months of treatment

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Difference in the number of recurrent hospitalizations due to heart failure between the treatment groups
recurrent hospitalizations due to heart failure
Difference in the number of hospitalizations for CV causes between the treatment groups
hospitalizations for CV causes
Difference in the number of hospitalizations for other than CV causes between the treatment groups
hospitalizations for other than CV causes
Time to adjudicated CV death
CV death
Time to adjudicated all cause death
all cause death
Time to adjudicated myocardial infarction
myocardial infarction
eGFR (Estimated Glomerular Filtration Rate) (CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration Equation)) creatine slope of change from baseline between the treatment groups
eGFR
Difference in the number of hospital re-admissions due to heart failure between the treatment groups
hospital re-admissions due to heart failure
Difference in the number of hospital re-admissions for any cause between the treatment groups
hospital re-admissions for any cause
Difference in the duration of hospital stay between the treatment groups after initiation of the study treatment
duration of hospital stay
Difference in the number of incidences of new onset AF and re-occurrence of AF between treatment groups
new onset AF
Difference in the change of ejection fraction in echocardiography between treatment groups
ejection fraction
Difference in the change of left ventricular diastolic function in echocardiography
left ventricular diastolic function
Difference in the change of LV strain analysis in echocardiography
LV strain
The time-averaged proportional change in NT-proBNP from
NT-proBNP
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
The time-averaged proportional change in pre-specified biomarkers
biomarkers
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

Full Information

First Posted
April 4, 2022
Last Updated
March 7, 2023
Sponsor
Medical University of Warsaw
Collaborators
Medical University of Vienna, Medical University of Graz, 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, Medical University of Gdansk, Autonomous Public Specialist Western John Paul II Hospital in Grodzisk Mazowiecki, Nicolaus Copernicus University in Toruń, Collegium Medicum in Bydgoszcz, Poznan University of Medical Sciences, 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
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1. Study Identification

Unique Protocol Identification Number
NCT05776043
Brief Title
Empagliflozin and Dapagliflozin in Patients Hospitalized for Acute Decompensated Heart Failure
Acronym
EMPATHY
Official Title
Empagliflozin and Dapagliflozin in Patients Hospitalized for Acute Decompensated Heart Failure (EMPATHY) - a Phase III Trial.
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 15, 2022 (Actual)
Primary Completion Date
September 30, 2024 (Anticipated)
Study Completion Date
December 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Medical University of Warsaw
Collaborators
Medical University of Vienna, Medical University of Graz, 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, Medical University of Gdansk, Autonomous Public Specialist Western John Paul II Hospital in Grodzisk Mazowiecki, Nicolaus Copernicus University in Toruń, Collegium Medicum in Bydgoszcz, Poznan University of Medical Sciences, 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

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Decompensated Heart Failure
Keywords
SGLT-2 inhibitors, dapagliflozin, empagliflozin, acute heart failure, decompensated heart failure

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Two arms with a subsequent stratification based on the SGLT2 inhibitor type.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
double blind
Allocation
Randomized
Enrollment
1364 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
SGLT 2 Inhibitor
Arm Type
Active Comparator
Arm Description
Empagliflozin (n=341) or Dapagliflozin (n=341): 9 months of treatment
Arm Title
Placebo with a switch to SGLT 2 Inhibitor
Arm Type
Placebo Comparator
Arm Description
Placebo (n=682) for 3 months of treatment with a subsequent switch to Empagliflozin (n=341) or Dapagliflozin (n=341): 6 months of treatment
Intervention Type
Drug
Intervention Name(s)
Empagliflozin 10 MG
Other Intervention Name(s)
Jardiance
Intervention Description
once daily for 6 or 9 months
Intervention Type
Drug
Intervention Name(s)
Dapagliflozin 10 MG
Other Intervention Name(s)
Forxiga
Intervention Description
once daily for 6 or 9 months
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Placebo with switch to SGLT2 inhibitor
Intervention Description
once daily for 3 months
Primary Outcome Measure Information:
Title
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)
Description
combined endpoint
Time Frame
at 3 and 9 months
Secondary Outcome Measure Information:
Title
Difference in the number of recurrent hospitalizations due to heart failure between the treatment groups
Description
recurrent hospitalizations due to heart failure
Time Frame
at 3 and 9 months
Title
Difference in the number of hospitalizations for CV causes between the treatment groups
Description
hospitalizations for CV causes
Time Frame
at 3 and 9 months
Title
Difference in the number of hospitalizations for other than CV causes between the treatment groups
Description
hospitalizations for other than CV causes
Time Frame
at 3 and 9 months
Title
Time to adjudicated CV death
Description
CV death
Time Frame
at 3 and 9 months
Title
Time to adjudicated all cause death
Description
all cause death
Time Frame
at 3 and 9 months
Title
Time to adjudicated myocardial infarction
Description
myocardial infarction
Time Frame
at 3 and 9 months
Title
eGFR (Estimated Glomerular Filtration Rate) (CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration Equation)) creatine slope of change from baseline between the treatment groups
Description
eGFR
Time Frame
at 3 and 9 months
Title
Difference in the number of hospital re-admissions due to heart failure between the treatment groups
Description
hospital re-admissions due to heart failure
Time Frame
at 3 and 9 months
Title
Difference in the number of hospital re-admissions for any cause between the treatment groups
Description
hospital re-admissions for any cause
Time Frame
at 3 and 9 months
Title
Difference in the duration of hospital stay between the treatment groups after initiation of the study treatment
Description
duration of hospital stay
Time Frame
at 3 and 9 months
Title
Difference in the number of incidences of new onset AF and re-occurrence of AF between treatment groups
Description
new onset AF
Time Frame
at 3 and 9 months
Title
Difference in the change of ejection fraction in echocardiography between treatment groups
Description
ejection fraction
Time Frame
at 3 and 9 months
Title
Difference in the change of left ventricular diastolic function in echocardiography
Description
left ventricular diastolic function
Time Frame
at 3 and 9 months
Title
Difference in the change of LV strain analysis in echocardiography
Description
LV strain
Time Frame
at 3 and 9 months
Title
The time-averaged proportional change in NT-proBNP from
Description
NT-proBNP
Time Frame
at 3 and 9 months
Title
The time-averaged proportional change in selected miRNA expression linked to hypertrophy, inflammation, fibrosis, apoptosis, electric stability between treatment groups and placebo group
Description
miRNA expression
Time Frame
at 3 and 9 months
Title
The time-averaged proportional change in pre-specified biomarkers
Description
biomarkers
Time Frame
at 3 and 9 months
Title
Change from baseline in clinical summary score (HF (Chronic Heart Failure) symptoms and physical limitations domains) of the Kansas City Cardiomyopathy Questionnaire (KCCQ)
Description
HF score
Time Frame
at 3 and 9 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Prof. Marek Postula, MD PhD
Phone
0048 22 1166160
Email
mpostula@wum.edu.pl
First Name & Middle Initial & Last Name or Official Title & Degree
Prof. Jolanta M. Siller-Matula, MD PhD
Email
Jolanta.Siller-Matula@meduniwien.ac.at
Facility Information:
Facility Name
Autonomous Public Specialist Western John Paul II Hospital
City
Grodzisk Mazowiecki
Country
Poland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Janusz Bednarski

12. IPD Sharing Statement

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Empagliflozin and Dapagliflozin in Patients Hospitalized for Acute Decompensated Heart Failure

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