EMPAGLIFLOZIN for Acute decompensated heart failure

Inclusion criteria

• {"criterion_text":"- Patients 18 years of age with the capacity to provide written informed consent\n- eGFR >20 ml/min/1,73m2\n- 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\n- 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).\n- Randomized no earlier than 24 hours and up to 10 days after initial presentation while still hospitalized\n- Stable as defined by: systolic blood pressure (SBP>100 mmHg for the preceding 6 hours)\n- No intensification of IV diuretics within the last 6 hours\n- No use of IV vasodilators within the last 6 hours\n- No use of IV inotropes or levosimendan within the last 24 hours prior to randomization\n- 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)."}

Exclusion criteria

• {"criterion_text":"- History of ketoacidosis\n- >1 episode of severe hypoglycaemia within the last 6 months under treatment with insulin or sulfonylurea\n- Acute symptomatic urinary tract infection or genital infection\n- Type 1 diabetes\n- SGLT-2 Inhibitor at baseline or known allergy to SGLT-2 Inhibitors\n- Current active cancer with less than 2 years of life expectancy\n- Pulmonary embolism, cerebrovascular accident as the primary trigger for the current hospitalization\n- 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\n- Any severe (obstructive or regurgitant) valvular heart disease, expected to lead to surgery during the trial period\n- Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant\n- Blood pH<7.32"}

Primary endpoints

• {"endpoint_text":"- Composite primary endpoint - time to first event of all-cause death or worsening HF (defined as worsening signs or symptoms of HF that require an intensification of diuretic therapy or any other intravenous therapy for HF or mechanical ventilatory, renal or circulatory support) or HF readmission (unplanned ambulatory visit or hospitalization due to symptoms of HF through 3 months).","definition_or_measurement_approach":"Time-to-event composite: time to first event of all-cause death OR worsening heart failure (worsening signs/symptoms requiring intensification of diuretic therapy or any other IV therapy for HF or mechanical ventilatory, renal or circulatory support) OR HF readmission (unplanned ambulatory visit or hospitalization due to HF symptoms) assessed through 3 months."}

Secondary endpoints

• {"endpoint_text":"- Composite endpoint - time to first event of all-cause death or worsening HF (defined as worsening signs or symptoms of HF that require an intensification of diuretic therapy or any other intravenous therapy for HF or mechanical ventilatory, renal or circulatory support) or HF readmission (unplanned ambulatory visit or hospitalization due to symptoms of HF through 9 months\n- Difference in the number of recurrent hospitalizations due to heart failure between the treatment groups: at 3 and 9 months\n- Difference in the number of hospitalizations for CV causes between the treatment groups: - time frame: at 3 and 9 months.\n- Difference in the number of hospitalizations for other than CV causes between the treatment groups: - time frame: at 3 and 9 months.\n- Time to adjudicate CV death- time frame: at 3 and 9 months.\n- Time to adjudicate all causes of death- time frame: at 3 and 9 months.\n- Time to adjudicate myocardial infarction- time frame: at 3 and 9 months\n- eGFR (Estimated Glomerular Filtration Rate) (CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration Equation)) CR slope of change from baseline: at 3 and 9 months\n- Difference in the number of hospital readmissions due to heart failure between the treatment groups- time frame: at 3 and 9 months\n- Difference in the number of hospital readmissions for any cause between the treatment groups- time frame: at 3 and 9 months\n- Difference in the duration of hospital stay between the treatment groups after initiation of the study treatment- time frame: at 3 and 9 months.\n- Difference in the number of incidences of new onset AF and re-occurrence of AF between treatment groups- time frame: at 3 and 9 months.\n- Difference in the change of ejection fraction in echocardiography between treatment groups from randomization to 3 and 9 months\n- Difference in the change of left ventricular diastolic function in echocardiography from randomization to 3 and 9 months.\n- Difference in the change of LV strain analysis in echocardiography from randomization to 3 and 9 months.\n- The time-averaged proportional change in NT-proBNP from baseline through 3 and 9 months.\n- Personalized medicine based on biomarker approach- the time-averaged proportional change in selected ncRNA expression linked to hypertrophy, inflammation, fibrosis, apoptosis, electric stability between treatment groups and placebo group from baseline through months 3 and 9.\n- Personalized medicine based on biomarker approach- the time-averaged proportional change in PCT- procalcitonin, ANP - atrial natriuretic peptide, FGF-23 - fibroblast growth factor-23, GDF-15 - growth differentiation factor-15, IL-2 - interleukin 2, IL-6 - interleukin 6 between treatment groups and placebo group from baseline through months 3 and 9.\n- Personalized medicine based on biomarker approach- association between primary and secondary clinical endpoints and microbiome metabolites at baseline in both treatment groups and placebo in long term follow-up (3 and 9 months).\n- Personalized medicine based on biomarker approach- association between primary and secondary clinical endpoints and metabolome at baseline in both treatment groups and placebo in long term follow-up (3 and 9 months).\n- Cost-effectiveness substudy.\n- Effect of SGLT-2 inhibitors according to clinical characteristics as age, gender.\n- Symptoms, Function, and Quality of Life substudy\n- Polypharmacy substudy\n- Effect of SGLT-2 inhibitors on cardiac muscle fibrosis based on magnetic resonance (MR) substudy.","definition_or_measurement_approach":"Secondary endpoints comprise time-to-event and count outcomes, adjudicated events (CV death, MI), rehospitalisation counts, changes in biomarkers and imaging measures. Time frames and specific measurement methods are provided per endpoint (mostly assessed at 3 and 9 months); eGFR slope by CKD-EPI, adjudication procedures for deaths/MI, echocardiography measures for EF/diastolic function/LV strain, biomarker assays for NT-proBNP, ncRNA, and listed biomarkers."}

Poland

Earliest CTIS Part Ii Submission Date

24-10-2024

Latest Decision Or Authorization Date

02-12-2024

Processing Time Days

39

Number Of Sites

19

Number Of Participants

1364

Primary sponsor

Full Name

Medical University Of Warsaw

Organisation Type

Educational Institution

Country Of Registered Address

Poland