Repetitive levosimendan infusions for patients with advanced chronic heart failure (LeoDOR)

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 264

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, betablocker, 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 after recompensation (= haemodynamically stable euvolemic, estab-lished on evidence-based oral medication and with
stable renal function for at least 24hrs before discharge) of 2500 ng/L (BNP 900 ng/L) and/or NYHA class III or IV at study entry.
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 132
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 132

Exclusion Criteria

1. Severe obstruction of ventricular outflow tracts such as haemodynamically significant uncorrected primary valve disease or hypertrophic cardiomyopathy or impaired ventricular filling such as restrictive cardiomyopathy.
2. Predominantly right heart failure a/o 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) <30 ml/min/1.73m2).
12. Anaemia (haemoglobin < 10 g/dl).
13. Significant hepatic impairment at the discretion of the investigator.
14. Hypersensitivity to levosimendan and any excipients.
15. Other serious diseases limiting life expectancy considerably (e.g. end-stage cancer, 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. (this may also apply to the trial subject’s partner
depending on the investigational product (IMP)). The following contraceptive methods with a Pearl Index lower than 1% are regarded as
highly-effective:
- Oral hormonal contraception (‘pill’) (as far as its efficacy is not expected to be impaired dur-ing the trial, e.g. with IMPs that cause vomiting and diarrhoea, adequate safety cannot be assumed)
- Dermal hormonal contraception
- Vaginal hormonal contraception (NuvaRing®)
- Contraceptive plaster
- Long-acting injectable contraceptives
- Implants that release progesterone (Implanon®)
- Tubal ligation (female sterilisation)
- Intrauterine devices that release hormones (hormone spiral)
- Double barrier methods.
This means that the following are not regarded as safe: condom plus spermicide, simple barrier methods (vaginal pessaries, condom, female condoms), copper spirals, the rhythm method, basal temperature method, and the withdrawal method (coitus interruptus).The regulations for contraception are derived from Guideline ICH E8 Chapter 3.2.2.1 Selection of subjects together with ICH M3 Note 4.
21. Person with any kind of dependency on the investigator, sponsor or clinical trial organizatio.
22. Person held in an institution by legal or official order.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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