Acute Decompensated Heart Failure
Conditions
Keywords
SGLT-2 inhibitors, dapagliflozin, empagliflozin, acute heart failure, decompensated heart failure
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.
Interventions
DRUGEmpagliflozin 10 MG
once daily for 6 or 9 months
DRUGDapagliflozin 10 MG
once daily for 6 or 9 months
DRUGPlacebo
once daily for 3 months
Sponsors
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 Hospital, Krakow
Ludwik Rydygier Regional Polyclinical Hospital in Toruń
University Teaching Hospital in Białystok
Medical University of Silesia in Katowice
Medical University of Warsaw
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
double blind
Intervention model description
Two arms with a subsequent stratification based on the SGLT2 inhibitor type.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) | at 3 and 9 months | combined endpoint |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Difference in the number of hospitalizations for CV causes between the treatment groups | at 3 and 9 months | hospitalizations for CV causes |
| Difference in the number of hospitalizations for other than CV causes between the treatment groups | at 3 and 9 months | hospitalizations for other than CV causes |
| Time to adjudicated CV death | at 3 and 9 months | CV death |
| Time to adjudicated all cause death | at 3 and 9 months | all cause death |
| Time to adjudicated myocardial infarction | at 3 and 9 months | 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 | at 3 and 9 months | eGFR |
| Difference in the number of hospital re-admissions due to heart failure between the treatment groups | at 3 and 9 months | hospital re-admissions due to heart failure |
| Difference in the number of hospital re-admissions for any cause between the treatment groups | at 3 and 9 months | hospital re-admissions for any cause |
| Difference in the number of recurrent hospitalizations due to heart failure between the treatment groups | at 3 and 9 months | recurrent hospitalizations due to heart failure |
| Difference in the number of incidences of new onset AF and re-occurrence of AF between treatment groups | at 3 and 9 months | new onset AF |
| Difference in the change of ejection fraction in echocardiography between treatment groups | at 3 and 9 months | ejection fraction |
| Difference in the change of left ventricular diastolic function in echocardiography | at 3 and 9 months | left ventricular diastolic function |
| Difference in the change of LV strain analysis in echocardiography | at 3 and 9 months | LV strain |
| The time-averaged proportional change in NT-proBNP from | at 3 and 9 months | 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 | at 3 and 9 months | miRNA expression |
| The time-averaged proportional change in pre-specified biomarkers | at 3 and 9 months | biomarkers |
| Change from baseline in clinical summary score (HF (Chronic Heart Failure) symptoms and physical limitations domains) of the Kansas City Cardiomyopathy Questionnaire (KCCQ) | at 3 and 9 months | HF score |
| Difference in the duration of hospital stay between the treatment groups after initiation of the study treatment | at 3 and 9 months | duration of hospital stay |
Countries
Poland
Contacts
Primary ContactProf. Marek Postula, MD PhD
Backup ContactProf. Jolanta M. Siller-Matula, MD PhD
Outcome results
None listed