RecruitingPhase 4NCT07105202

Shorter Weaning From Invasive Ventilation With Levosimendan

Shorter Weaning From Invasive Ventilation With Levosimendan: a Randomized, Double-blind, Multicentre Study in Critically Ill Patients

Sponsor

Radboud University Medical Center

Enrollment

250 participants

Start Date

Sep 17, 2025

Study Type

INTERVENTIONAL

Conditions

Mechanical Ventilation Weaning Failure

Summary

Prolonged weaning from mechanical ventilation is a common and serious challenge in the ICU, associated with increased morbidity, mortality, and length of stay. Diaphragm dysfunction plays a key role in weaning failure, and current strategies to support respiratory muscle function are limited. Levosimendan is a calcium sensitizer that enhances cardiac and skeletal muscle contractility, including the diaphragm, without increasing oxygen demand. The investigators hypothesize that treatment with Levosimendan in difficult-to-wean ICU patients will improve diaphragm function and thereby shorten the duration of mechanical ventilation compared to placebo.

Eligibility

Min Age: 18 Years

Inclusion Criteria4

Invasively ventilated \> 48 hours.
Failed at least one spontaneous breathing trial (SBT).
Age above 18 years.
Female patients with age \< 60 must have a negative pregnancy test (blood or urine) prior to participation.

Exclusion Criteria7

Pre-existing neuromuscular disease (congenital or acquired)
Endotracheally intubated primarily for neurological reason (e.g., traumatic brain injury, intracranial haemorrhage, epilepsy, intracranial infection), or developed severe intracranial haemorrhage/infarction during ICU stay.
Contra-indications for levosimendan: severe renal failure (creatinine clearance \<30mL/min) unless managed with appropriate continuous kidney replacement therapy (such as CRRT), severe liver failure (Child-Pugh class C), history of torsade des pointes; known significant mechanical obstructions affecting ventricular filling/ outflow or both; prolonged QTc interval (QTc \> 470ms); breast feeding; known hypersensitivity to levosimendan.
Treatment with intermittent haemodialysis.
Treatment limitation decision in place: do not reintubate
Previous treatment with levosimendan within 30 days.
Currently in another interventional trial that might interact with study drug or primary outcome.

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Interventions

DRUGlevosimendan

Participants randomized to to the intervention will receive levosimendan. The infusion is administered over 24 hours, starting at a dose of 0.1 µg/kg/min. After 4 hours, the dose may be increased to 0.2 µg/kg/min if tolerated, based on clinical judgment. A maximum of four treatment cycles may be given if the patient is not successfully weaned from mechanical ventilation within 7 days.

DRUGSoluvit

Participants randomized to this arm will receive a placebo consisting of Soluvit diluted in glucose 5%, administered as an intravenous infusion over 24 hours. The infusion will mimic the Levosimendan administration protocol, starting at 0.1 µg/kg/min and potentially increasing to 0.2 µg/kg/min after 4 hours, to maintain blinding. A maximum of four placebo treatment cycles may be administered if the patient is not successfully weaned from mechanical ventilation within 7 days.

OTHERStandard care

All patients in this arm will receive standard ICU care, including daily assessments for readiness to wean from invasive ventilation.