Repetitive Levosimendan Infusion for Patients With Advanced Chronic Heart Failure

NCT03437226 | Unknown Phase 3 DMC

• 1 other identifier: LeoDOR2017
• Study Type: interventional
• Target: 264
• Locations: 1 country
• Sites: 1

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

Keywords

Heart Failure, Levosimendan

Outcome Measures

Primary Outcomes (2)

• Time to death, high-urgent heart transplantation or ventricular assist device (VAD), time to non-fatal HF event

  Time to event in days, from baseline visit (day 1) up to Follow-up 2 (day 180)

  From baseline (day 1) up to Follow-up 2 (day 180)

• Change in NT-proBNP

  pg/ml

  Change from Baseline NT-proBNP (day 1) to Follow-up 1 (day 90)

Secondary Outcomes (8)

• Change in functional status and symptoms via KCCQ (Combined Outcome measurement)

  From baseline (day 1) up to day 98 (FUP 1)

• Change in functional status and symptoms via PGA (Combined Outcome measurement)

  From baseline (day 1) up to day 98 (FUP 1)

• Change in functional status and symptoms via EQ-5D-5L (Combined Outcome measurement)

  From baseline (day 1) up to day 98 (FUP 1)

• cumulative number of: days alive out of hospital (Combined Outcome measurement)

  From baseline (day 1) up to day 180 (FUP 2)

• cumulative number of: non-fatal HF events (Combined Outcome measurement)

  From baseline (day 1) up to day 180 (FUP 2)

Study Arms (2)

Levosimendan Arm

EXPERIMENTAL

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

Drug: Levosimendan 2.5 MG/ML

Placebo Arm

PLACEBO COMPARATOR

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

Drug: Placebos

Interventions

Levosimendan 2.5 MG/ML 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.

Also known as: Simdax, Orion Pharma, Espoo, Finland

Levosimendan Arm

Placebos 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.

Also known as: Placebo Levosimendan infusion concentrate

Placebo Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written, signed and dated informed consent.
• Male and female patients over 18 years of age.
• 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.
• 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).
• Left ventricular ejection fraction less than or equal to 30% as assessed by echocardiography, radionuclide ventriculography or contrast angiography within the index hospitalisation.
• Currently hospitalised for decompensated HF requiring i.v. diuretics, or i.v. vasodilators, or i.v. inotropic therapy, or their combination.
• 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.
• 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

You may not qualify if:

• 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.
• Predominantly right heart failure a/o severe tricuspid regurgitation
• Cardiac surgery or coronary angioplasty within 30 days before study drug initiation.
• Acute coronary syndrome within 30 days before study drug initiation.
• Patients who are scheduled for cardiac surgery or angioplasty in the next 3 months
• History of torsades de pointes
• Stroke or transient ischaemic attack (TIA) within 3 months before study drug initiation
• Systolic blood pressure less than 90 mmHg at baseline
• Heart rate 120 bpm or greater at baseline
• Serum potassium less than 3.5 mmol/l before study drug initiation.
• Severe renal insufficiency (estimated glomerular filtration rate (eGFR) \<30 ml/min/1.73m2)
• Anaemia (haemoglobin \< 10 g/dl)
• Significant hepatic impairment at the discretion of the investigator.
• Hypersensitivity to levosimendan
• Other serious diseases limiting life expectancy considerably (e.g. end-stage cancer, end-stage lung disease)

Sponsors & Collaborators

• Dr. Gerhard Pölzl: lead
• Orion Corporation, Orion Pharma: collaborator

Study Sites (1)

Medical University Innsbruck

Innsbruck, Tyrol, 6020, Austria

RECRUITING

MeSH Terms

Conditions

Heart Failure

Interventions

Simendan

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Hydrazones; Hydrazines; Organic Chemicals; Pyridazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Central Study Contacts

Kathrin Becker, PhD.

CONTACT

+43512900371; leodor@i-med.ac.at

Sabine Embacher-Aichhorn

CONTACT

+435129003700; leodor@i-med.ac.at

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Univ. Prof. Dr. med.

Study Record Dates

• First Submitted: October 9, 2017
• First Posted: February 19, 2018
• Study Start: March 8, 2018
• Primary Completion: April 1, 2019
• Study Completion: December 31, 2019
• Last Updated: August 22, 2018

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)