Clinical trial NCT05776043: Empagliflozin and Dapagliflozin in Patients Hospitalized for Acute Decompensated Heart Failure
Official title: Empagliflozin and Dapagliflozin in Patients Hospitalized for Acute Decompensated Heart Failure (EMPATHY) - a Phase III Trial.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Acute Decompensated Heart Failure
Keywords: SGLT-2 inhibitors
dapagliflozin
empagliflozin
acute heart failure
decompensated heart failure
Lead sponsor: Medical University of Warsaw
Sponsor class: OTHER
Collaborators: name: Medical University of Vienna
name: Medical University of Graz
name: University Clinical Center of the Medical University of Warsaw
name: Jerzy Popiełuszko Bielański Hospital in Warsaw
name: Regional Polyclinical Hospital in Kielce
name: University Clinical Hospital Military Medical Academy, Central Veterans Hospital in Łódź
name: Medical University of Gdansk
name: Autonomous Public Specialist Western John Paul II Hospital in Grodzisk Mazowiecki
name: Nicolaus Copernicus University in Toruń, Collegium Medicum in Bydgoszcz
name: Poznan University of Medical Sciences
name: John Paul II Specialist Hospital in Kraków
name: Ludwik Rydygier Regional Polyclinical Hospital in Toruń
name: University Teaching Hospital in Białystok
name: Medical University of Silesia in Katowice
First posted: 2023-03-20
Enrollment: 1364
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Two arms with a subsequent stratification based on the SGLT2 inhibitor type.
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: 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)
timeFrame: at 3 and 9 months
Secondary outcomes:
measure: Difference in the number of recurrent hospitalizations due to heart failure between the treatment groups
timeFrame: at 3 and 9 months
measure: Difference in the number of hospitalizations for CV causes between the treatment groups
timeFrame: at 3 and 9 months
measure: Difference in the number of hospitalizations for other than CV causes between the treatment groups
timeFrame: at 3 and 9 months
measure: Time to adjudicated CV death
timeFrame: at 3 and 9 months
measure: Time to adjudicated all cause death
timeFrame: at 3 and 9 months
measure: Time to adjudicated myocardial infarction
timeFrame: at 3 and 9 months
measure: eGFR (Estimated Glomerular Filtration Rate) (CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration Equation)) creatine slope of change from baseline between the treatment groups
timeFrame: at 3 and 9 months
measure: Difference in the number of hospital re-admissions due to heart failure between the treatment groups
timeFrame: at 3 and 9 months
measure: Difference in the number of hospital re-admissions for any cause between the treatment groups
timeFrame: at 3 and 9 months
measure: Difference in the duration of hospital stay between the treatment groups after initiation of the study treatment
timeFrame: at 3 and 9 months
measure: Difference in the number of incidences of new onset AF and re-occurrence of AF between treatment groups
timeFrame: at 3 and 9 months
measure: Difference in the change of ejection fraction in echocardiography between treatment groups
timeFrame: at 3 and 9 months
measure: Difference in the change of left ventricular diastolic function in echocardiography
timeFrame: at 3 and 9 months
measure: Difference in the change of LV strain analysis in echocardiography
timeFrame: at 3 and 9 months
measure: The time-averaged proportional change in NT-proBNP from
timeFrame: at 3 and 9 months
measure: The time-averaged proportional change in selected miRNA expression linked to hypertrophy, inflammation, fibrosis, apoptosis, electric stability between treatment groups and placebo group
timeFrame: at 3 and 9 months
measure: The time-averaged proportional change in pre-specified biomarkers
timeFrame: at 3 and 9 months
measure: Change from baseline in clinical summary score (HF (Chronic Heart Failure) symptoms and physical limitations domains) of the Kansas City Cardiomyopathy Questionnaire (KCCQ)
timeFrame: at 3 and 9 months
Other outcomes:
Locations:
city: Grodzisk Mazowiecki
country: Poland
facility: Autonomous Public Specialist Western John Paul II Hospital
Study officials:
References: