Repetitive Levosimendan Infusion for Patients With Advanced Chronic Heart Failure

NCT ID: NCT03437226

Last Updated: 2018-08-22

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 264 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-03-08
• Study Completion Date: 2019-12-31

Brief Summary

Repetitive levosimendan infusions for patients with advanced chronic heart failure (LeoDOR) A randomised, double-blind, placebo-controlled multicentre study with parallel group design.

Mortality and rehospitalisation rates are high in the vulnerable phase following heart failure hospitalisation. Previous studies suggest that these events can be reduced by repeat infusions of levosimendan in patients with advanced heart failure.

Conditions

Heart Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Levosimendan Arm

Patients receive 6 or 24 hours infusion depending on the site. Levosimendan 2.5 MG/M 6h infusion group: 0,2 μg/kg/min 7 times (day 0, 14, 28, 42, 56, 70, 84) Levosimendan 24h infusion group: 0,1 μg/kg/min 5 times (day 0, 21,42,63,84) Levosimendan

Group Type: EXPERIMENTAL

Levosimendan 2.5 MG/ML

Intervention Type: DRUG

Levosimendan Arm: 1 x 5 ml (1 vial) of levosimendan infusion concentrate is added to one 250 ml infusion bag of 5% glucose or 0.9% NaCl in diabetic patients.

Placebo Arm

Patients receive 6 or 24 hours infusion depending on the site. 6h infusion group: 0,2 μg/kg/min 7 times (day 0, 14, 28, 42, 56, 70, 84) Placebo 24h infusion group: 0,1 μg/kg/min 5 times (day 0, 21,42,63,84) Placebo

Group Type: PLACEBO_COMPARATOR

Placebos

Intervention Type: DRUG

Placebo Arm: 1 x 5 ml (1 vial) of placebo levosimendan infusion concentrate is added to one 250 ml infusion bag of 5% glucose or 0.9% NaCl in diabetic patients.

Interventions

Levosimendan 2.5 MG/ML

Levosimendan Arm: 1 x 5 ml (1 vial) of levosimendan infusion concentrate is added to one 250 ml infusion bag of 5% glucose or 0.9% NaCl in diabetic patients.

Intervention Type: DRUG

Placebos

Placebo Arm: 1 x 5 ml (1 vial) of placebo levosimendan infusion concentrate is added to one 250 ml infusion bag of 5% glucose or 0.9% NaCl in diabetic patients.

Intervention Type: DRUG

Other Intervention Names

Simdax, Orion Pharma, Espoo, Finland; Placebo Levosimendan infusion concentrate

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Orion Corporation, Orion Pharma

INDUSTRY

Sponsor Role: collaborator

Dr. Gerhard Pölzl

OTHER

Sponsor Role: lead

Responsible Party

Dr. Gerhard Pölzl

Univ. Prof. Dr. med.

Responsibility Role: SPONSOR_INVESTIGATOR

Locations

Medical University Innsbruck

Innsbruck, Tyrol, Austria

Site Status: RECRUITING

Countries

Austria

Central Contacts

Kathrin Becker, PhD.

Role: CONTACT

leodor@i-med.ac.at

+43512900371 ext. 844

Sabine Embacher-Aichhorn

Role: CONTACT

leodor@i-med.ac.at

+435129003700 ext. 86

Facility Contacts

Kathrin Becker, PhD

Role: primary

leodor@i-med.ac.at

+43512900371 ext. 844

Sabine Embache-Aichhorn

Role: backup

leodor@i-med.ac.at

+43512900370 ext. 086

Other Identifiers

LeoDOR2017

Identifier Type: -

Identifier Source: org_study_id