I50
Conditions
Interventions
12 weeks treatment period
Group 1: 6-hour infusion every 2 weeks with levosimendan at 7 treatment visits every 2 weeks
i.v. treatment with an infusion rate of 0.2 µg/kg/min
12 weeks treatment period
Group 2: 24-hour infusion every 3 weeks with levosimendan
at 5 treatment visits every 3 weeks
12 weeks treatment period
Group 3: 6-hour infusion every 2 weeks with levosimendan at 7 treatment visits every 2 weeks
12 weeks treatment period
Group 4: 24-hour infusion every 3 weeks with placebo at 5 treatment visits every 3 weeks
Sponsors
Medizinische Universität Innsbruck
Eligibility
Sex/Gender
All
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Written, signed and dated informed consent. 2. Male and female patients over 18 years of age. 3. Women of childbearing potential must have a monthly negative pregnancy test and must refrain from breastfeeding. Women who are postmenopausal (1 year since last menstrual cycle), surgically sterilised or who have undergone a hysterectomy are considered not to be of childbearing potential. 4. CHF diagnosed at least 6 months before screening and treated with individually optimised long-term oral treatment for the last month, unless not tolerated (e.g., ACE-inhibitor or AT II blocker, beta-blocker, mineralocorticoid receptor antagonist, angiotensin II receptor blocker neprilysin inhibitor [ARNI] and with devices [e.g., CRT/ICD], as needed). 5. Left ventricular ejection fraction less than or equal to 30% as assessed by echocardiography, radionuclide ventriculography or contrast angiography within the index hospitalisation. 6. Currently hospitalised for decompensated HF requiring i.v. diuretics, or i.v. vasodilators, or i.v. inotropic therapy, or their combination. 7. Previous hospitalisation or visit to outpatient clinic requiring i.v. diuretics, i.v. vasodilators, or i.v. inotropic therapy, or their combination for acute decompensated HF within 12 months before the current hospitalisation. 8. NT-proBNP level (as measured by the local laboratory) after recompensation of 2500 ng/L (BNP 900 ng/L) and/or NYHA class III or IV at study entry.
Exclusion criteria
Exclusion criteria: 1. Severe obstruction of ventricular outflow tract such as haemodynamically significant uncorrected primary valve disease or hypertrophic cardiomyopathy or impaired ventricular filling such as restrictive cardiomyopathy 2. Predominantly right heart failure and/or severe tricuspid regurgitation 3. Cardiac surgery or coronary angioplasty within 30 days before study drug initiation 4. Acute coronary syndrome within 30 days before study drug initiation 5. Patients who are scheduled for cardiac surgery or angioplasty in the next 3 months 6. History of torsades de pointes 7. Stroke or transient ischaemic attack (TIA) within 3 months before study drug initiation 8. Systolic blood pressure less than 90 mmHg at baseline 9. Heart rate 120 bpm or greater at baseline 10. Serum potassium less than 3.5 mmol/l before study drug initiation 11. Severe renal insufficiency (estimated glomerular filtration rate [eGFR] less than 30 ml/min/1.73m2) 12. Anaemia (haemoglobin less than 10 g/dl) 13. Significant hepatic impairment at the discretion of the investigator 14. Hypersensitivity to levosimendan 15. Other serious diseases limiting life expectancy considerably (e.g. end-stage cancer, end-stage renal disease, end-stage lung disease) 16. Participation in a clinical trial with any experimental treatment within 30 days prior to screening or previous participation in the present study 17. Administration of levosimendan within 14 days prior the study drug initiation (the first study drug application has to be postponed for at least 14 days after the end of this premedication) 18. Suspected non-compliance 19. Pregnant woman and nursing mother 20. Failure to use highly effective (Pearl Index lower than 1%) contraceptive methods 21. Person with any kind of dependency on the investigator 22. Person held in an institution by legal or official order
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The hypothesis will be tested based on a global rank endpoint in which all participants are ranked across three hierarchical groups: 1. time to death or high-urgent heart transplantation or ventricular assist device (VAD), 2. time to non-fatal HF event (see section 1.1) requiring i.v. vasoactive therapy (i.v. diuretics, i.v. vasodilators or i.v. inotropes – either inhospital or ambulatory in an emergency department) and time-averaged proportional change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) from baseline to 14 weeks. | — |
Secondary
| Measure | Time frame |
|---|---|
| Individual components of the primary endpoint at 14 weeks and 26 weeks -time to death / high-urgent heart transplantation / VAD implantation at 14 weeks and 26 weeks -time to non-fatal HF event defined as an episode requiring i.v. vasoactive therapy (i.v. diuretic, i.v. inotropic) at week 14 and 26 -time-averaged proportional change in NT-proBNP from baseline to 14 weeks 2. Change in functional status - 6-minute walk test at baseline and 14 weeks -New York Heart Association (NYHA) class at baseline and 14weeks 3. Change in symptoms - Kansas City Cardiomyopathy Questionnaire (KCCQ) – clinical summary score - from baseline to 14 weeks - Difference in patient global assessment (PGA) from baseline to 14 weeks 4. Number of combined events - death / heart transplantation / VAD implantation / non-fatal HF event 5. Cumulative number of non-fatal HF events 6. Cumulative number of hospital admissions (AHF vs. cardiovascular admissions vs. non-cardiovascular admissions) 7. Cumulative days alive and out of hospital 8. Cumulative number of death and total (first and recurrent) non-fatal HF events 9. Safety assessment Additional endpoints: 1. Changes in background medication 2. Cost-effectiveness (EQ-5D-5L VAS) 3. Changes in biomarkers | — |
Countries
Austria, Denmark, Finland, Germany, Hungary, Italy, Slovenia, Spain, Sweden, Switzerland
Contacts
Public ContactStefan Störk
University Hospital Würzburg
Outcome results
None listed