REPETITIVE LEVOSIMENDAN INFUSIONSFOR PATIENTS WITH ADVANCED CHRONIC HEART FAILURE

Recruitment & Eligibility

Status: Complete

Sex: All

Target Recruitment: 149

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

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

Study & Design

Study Type: interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
The hypothesis will be tested based on a global rank endpoint in which<br>all participants are ranked across three hierarchical groups:<br>1. time to death or high-urgent heart transplantation or ventricular<br>assist device (VAD),<br>2. time to non-fatal HF event (see section 1.1) requiring i.v. vasoactive<br>therapy (i.v. diuretics, i.v. vasodilators or i.v. inotropes – either inhospital<br>or ambulatory in an emergency department) and time-averaged proportional change in N-terminal pro-B-type<br>natriuretic peptide (NT-proBNP) from baseline to 14 weeks.

Secondary Outcome Measures

Name	Time	Method

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