Patients with acute heart failure
Conditions
Interventions
Trade Name: Jardiance
Product Name: Empagliflozin
Product Code: BI 10773
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Empagliflozin
CAS Number: 864070-44-0
Concentration unit: mg milli
Sponsors
RWTH Aachen University represented by the Rector, himself, represented by the Dean of the Medical Faculty
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age = 18 years 2. Patients with acute heart failure with associated signs or symptoms (dyspnea on exertion, orthopnea, paroxysmal dyspnea, peripheral oedema, chest x-ray with pulmonary congestion) 3. Serum levels of NT-proBNP = 1000 pg/ml within 48 hours of informed consent 4. Written informed consent prior to study participation Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 11 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 45
Exclusion criteria
Exclusion criteria: 1. Type 1 diabetes 2. Participants of child-bearing age without adequate contraception 3. Pregnancy or lactating females 4. Cardiogenic shock 5. Acute coronary syndrome within 30 days prior to randomization 6. Planned or recent percutaneous or surgical coronary intervention within 30 days prior to randomization 7. Signs of ketoacidosis and/or hyperosmolar hyperglycemic syndrome (pH = 7.30 and glucose >14 mmol/l and HCO3- = 18 mmol/l) 8. uncontrolled active infection 9. Primary cause of dyspnea due to non-cardiac, non-HF causes such as acute or chronic respiratory disorders 10. Coronary artery disease with planned revascularization within the study period 11. Renal impairment (GFR 3 mg/dL) or history of cirrhosis with evidence of portal hypertension (e.g., presence of esophageal varices) 13. Uncontrolled thyroid disease 14. Uncontrolled Endocrinopathies like Graves’ disease, acromegaly, Cushings’ disease 15. Hypertensive retinopathy or encephalopathy 16. Bariatric surgery in last 2 years prior to randomization 17. Patients in whom study participation is not deemed appropriate under consideration of clinical wellbeing by the principal investigator 18. The subject is mentally or legally incapacitated 19. The subject received an investigational drug within 30 days prior to inclusion into this study 20. Urinary tract infections or significant formation of residual urine in medical history 21. Patients with particular risk for ketoacidosis (alcohol abuse, pancreatitis, pancreatic insulin deficiency from any cause, caloric restriction etc.) or ketoacidosis in the past 22. Frequent hypoglycaemic events (in the opinion of the investigator) 23. Intolerance to Empagliflozin and excipients in Empagliflozin or rather placebo 24. Patients with severe stenosis or regurgitation of the aortic, pulmonary or mitral valve
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To examine the effect of Empagliflozin 10mg qd versus placebo on cardiac output in patients with acute heart failure. ;Secondary Objective: Effect of Empagliflozin on systemic vascular resistance, stroke volume, left ventricular systolic and diastolic function, exercise capacity, patient-reported dyspnea, peak expiratory flow rate, clinical judged diuretic requirement, heart rate variability, percentage of supraventricular and ventricular contraction of total heart beats, NT-proBNP, eGFR, cystatin c, kidney injury risk score (defined by TIMP-2 x IGFBP7), sodium excretion and metabolic parameters (glucagon, insulin, total-ketone bodies, -hydroxybutyrate, etc.) in patients with acute heart failure;Primary end point(s): Effect of Empagliflozin 10 mg once daily on cardiac output by ClearSight System in comparison to placebo ;Timepoint(s) of evaluation of this end point: Baseline and 6 hours, day 1, 3, 7 and 30 following treatment initiation | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Most important secondary endpoints: Effect of Empagliflozin 10 mg once daily on - Systemic vascular resistance (ClearSight System) - Stroke volume (ClearSight System) - Exercise capacity (Hand grip) - Patient-reported dyspnea (visual analogue scale (VAS), 7 point categorical Likert scale) - Peak expiratory flow rate - Oxygen saturation (%) - Respiratory rate (breaths/min) - Oxygen delivered (l/min) - Clinical judged diuretic requirement - Diuretic response (defined as ? weight kg/[(total i.v. dose)/40mg]+[(total oral dose)/80mg)] furosemide (or equivalent loop diuretic dose) - Serum NT-proBNP - Kidney injury risk score by NephroCheck® (defined by TIMP-2 x IGFBP7 in urine) - eGFR - Serum Cystatin C - Lactate, pH, HCO3- - Blood pressure - Heart rate - Heart rate variability (24 h ECG) - Percent of supraventricular and ventricular contraction of total heart beats (24 h ECG) - Body weight - Urinary volume - Sodium excretion in 24 h urine collection (osmolarity, sodium, creatine, chloride, potassium, creatine-clearance, protein, urea nitrogen, magnesium, phosphate, glucose, calcium, uric acid) - Serum osmolarity, potassium, chloride - Serum levels of glucose, glucagon, insulin, total-ketone bodies, ß-hydroxybutyrate, aldosterone, free fatty acids - Hemoglobin, haematocrit, erythropoietin levels in comparison to placebo at baseline and 6 hours, day 1, 3, 7 and 30 following treatment initiation. Effect of Empagliflozin 10 mg once daily on - Microbiome analysis in comparison to placebo at baseline after 7 and 30 days of treatment Effect of Empagliflozin 10 mg once daily on - Left ventricular systolic function (ejection fraction) - Left ventricular diastolic function (2D and 3D parameter global strain rate E by echocardiography and by standardized parameter E/E’ and left atrial (LA) volume) in comparison to placebo at baseline after 30 days of treatment.;Timepoint(s) of evaluation of this end point: at baseline and after 6 hours, day 1, 3, 7 and | — |
Countries
Germany
Contacts
Public ContactClinical Trial Center
Center for Transitional & Clinical Research Aachen (CTC-A)
Outcome results
None listed