Interest of Levosimendan in Reducing Weaning Failures of ExtraCorporeal Life Support - ECLS (Weanilevo)

Interest of Levosimendan in Reducing Weaning Failures of ExtraCorporeal Life Support - ECLS. Randomized, Controlled, Multicenter, Double-blind, Multicenter Clinical Trial

Extracorporeal life support (ECLS) is a circulatory cardio supplementation technique; it therefore makes it possible to compensate for a defective cardiac or cardio-respiratory function. ECLS nevertheless remains a temporary assistance technique pending a potential recovery of cardiac function, or it can be used to direct patients towards a heart transplant or long-term circulatory assistance (Left Ventricular Assist Device (LVAD) or Total Heart). In patients with complete or partial recovery of cardiac and circulatory function, ECLS withdrawal may be considered. Withdrawal from ECLS remains a delicate phase and the risk of failure is high. The mechanism of action of levosimendan, a drug that increases the contractility of the heart, suggests that it would improve the heart-vessel connection and reduce the rate of ECLS withdrawal failure. The effect of levosimendan is maximal 24 to 48 hours after the end of the infusion and has a prolonged period of action.

The objective is to evaluate the efficacy of levosimendan administration (0.2 µg/kg/min over 24 hours) - versus placebo - prior to ECLS removal on the rate of withdrawal failure in patients under ECLS.

Study Overview

• Status: Recruiting
• Conditions: Acute Decompensated Heart Failure
• Intervention / Treatment: Drug: Levosimendan; Drug: Cernevit

• Study Type: Interventional
• Enrollment (Anticipated): 210
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Mohamed Omar ELLOUZE; Phone Number: +33 03.80.29.32.62; Email: mohamedomar.ellouze@chu-dijon.fr

Study Locations

• France
  • Dijon, France, 21079
    • Recruiting
    • Chu Dijon Bourgogne
    • Contact: Mohamed Omar ELLOUZE; Phone Number: +33 03 80 29 32 62; Email: mohamedomar.ellouze@chu-dijon.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• adult patient
• patient or person responsible for the patient has given written consent
• patient with acute circulatory heart failure under ECLS

• patient meeting criteria for ECLS withdrawal

  • ECLS flow rate at 1.0-1.5l/min and/or ECLS pump rpm ≤ 1500 rpm
  • LVEF > 20% in cardiac ultrasound and aortic ITV > 10 cm
  • VIS score ≤ 10
  • Arterial lactates ≤ 2 mmol/l
  • Right ventricular outflow tract shortening fraction > 30%
  • Basal diameter at the tricuspid telediastolic ring of the right ventricle < 35 mm
  • Fraction of inspired oxygen combined between ventilator and ECLS < 80%
• ECLS withdrawl scheduled within 48 hours
• Absence of an initial or progressive infectious episode (no planned introduction of antibiotic therapy within 48 hours prior to inclusion)

Exclusion Criteria:

• Patient with hepatic insufficiency: cytolysis at least 20 times normal
• Drug intoxication and attempted suicide

• Patient with a contraindication to the use of levosimendan:

  • hypersensitivity to the active substance or any of the excipients
  • severe hypotension and ventricular tachycardia
  • significant mechanical obstructions affecting ventricular filling and/or ejection
  • severe renal failure (creatinine clearance < 30 ml/min)
  • severe liver failure (TP<50%)
  • history of torsades de pointes

• Patient with a contraindication to the use of CERNEVIT®:

  • hypersensitivity to active substances, in particular to vitamin B1 or to one of the excipients or to soy protein products or to peanut protein products
  • hypervitaminosis to any vitamin contained in this formulation
  • severe hypercalcemia, hyper calciuria, tumour, bone metastasis, primary hyperparathyroidism, granulomatosis
• patient not affiliated to or not benefiting from national health insurance
• patient subject to legal protection (curatorship, guardianship)
• patient subject to limited judicial protection
• pregnant, parturient or breastfeeding woman

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: Placebo	Drug: Cernevit; mixture of 12 vitamins The dilution of the treatment is done in a 500ml bag of 5% Glucose The product is administered as a continuous infusion for 24 hours at an initial rate of 0.2 µg/kg/min
Experimental: Levosimendan	Drug: Levosimendan; Levosimendan 2.5mg/ml, solution to be diluted for infusion Dilution in a 500ml bag of 5% Glucose The product is administered as a continuous infusion for 24 hours at an initial rate of 0.2 µg/kg/min

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ECLS withdrawal failure	Withdrawal failure is defined as the absence of ECLS discontinuation within 48 hours of randomization or the use of temporary circulatory assistance such as ECLS, Impella® pump or intra-aortic balloon pump (IABP) or death	7 days after ECLS removal

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire Dijon

Study record dates

Study Major Dates

• Study Start (Actual): February 24, 2020
• Primary Completion (Anticipated): February 1, 2023
• Study Completion (Anticipated): February 1, 2024

Study Registration Dates

• First Submitted: November 7, 2019
• First Submitted That Met QC Criteria: November 7, 2019
• First Posted (Actual): November 12, 2019

Study Record Updates

• Last Update Posted (Actual): April 29, 2021
• Last Update Submitted That Met QC Criteria: April 27, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Enzyme Inhibitors; Protective Agents; Cardiotonic Agents; Phosphodiesterase Inhibitors; Phosphodiesterase 3 Inhibitors; Simendan
• Other Study ID Numbers: ELLOUZE_ORION_2018

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No