Repetitive Levosimendan Infusion for Patients With Advanced Chronic Heart Failure

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03437226
• Date of registration: 09/10/2017
• Prospective Registration: Yes
• Primary sponsor: Dr. Gerhard Pölzl
• Public title: Repetitive Levosimendan Infusion for Patients With Advanced Chronic Heart Failure LeoDOR
• Scientific title: Repetitive Levosimendan Infusion for Patients With Advanced Chronic Heart Failure
• Date of first enrolment: March 8, 2018
• Target sample size: 264
• Recruitment status: Unknown status
• URL: https://clinicaltrials.gov/show/NCT03437226
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Care Provider, Investigator).
• Phase: Phase 3

Countries of recruitment

Austria

Contacts

• Name: Kathrin Becker, PhD

• Name: Kathrin Becker, PhD.

Key inclusion & exclusion 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 after recompensation of more or equal 2500 ng/L (BNP more or equal 900
ng/L) and/or NYHA class III or IV at study entry

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

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.

21. Person with any kind of dependency on the investigator

22. Person held in an institution by legal or official order



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Heart Failure

Intervention(s)

Drug: Levosimendan 2.5 MG/ML

Drug: Placebos

Primary Outcome(s)

Change in NT-proBNP [Time Frame: Change from Baseline NT-proBNP (day 1) to Follow-up 1 (day 90)]

Time to death, high-urgent heart transplantation or ventricular assist device (VAD), time to non-fatal HF event [Time Frame: From baseline (day 1) up to Follow-up 2 (day 180)]

Secondary Outcome(s)

death [Time Frame: From baseline (day 1) to day 180 (FUP 2)]

cumulative number of: hospital admissions (Combined Outcome measurement) [Time Frame: From baseline (day 1) up to day 180 (FUP 2)]

Change in functional status and symptoms via EQ-5D-5L (Combined Outcome measurement) [Time Frame: From baseline (day 1) up to day 98 (FUP 1)]

cumulative number of: days alive out of hospital (Combined Outcome measurement) [Time Frame: From baseline (day 1) up to day 180 (FUP 2)]

Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) [Time Frame: From baseline (day 1) to day 180 (FUP 2)]

Change in functional status and symptoms via PGA (Combined Outcome measurement) [Time Frame: From baseline (day 1) up to day 98 (FUP 1)]

cumulative number of: non-fatal HF events (Combined Outcome measurement) [Time Frame: From baseline (day 1) up to day 180 (FUP 2)]

Change in functional status and symptoms via KCCQ (Combined Outcome measurement) [Time Frame: From baseline (day 1) up to day 98 (FUP 1)]

Secondary ID(s)

LeoDOR2017

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Orion Corporation, Orion Pharma