Using levosimendan to shorten time on a ventilator

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

This will test whether giving levosimendan to adults in the ICU who have failed a breathing trial helps them get off the ventilator sooner.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 250 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Radboud University Medical Center (Academic / other)
• Locations: 8 sites (Arnhem, Gelderland and 7 other locations)
• Trial ID: NCT07105202 on ClinicalTrials.gov

What this trial studies

WEANLESS is a multicenter, double-blind, randomized trial enrolling 250 adults who have been invasively ventilated for more than 48 hours and failed at least one spontaneous breathing trial. Participants are randomized to a 24-hour continuous infusion of levosimendan (with a possible second dose escalation and up to four cycles if needed) or placebo, in addition to standard ICU care. The main outcome is ventilator-free days alive at day 28, and secondary follow-up includes quality-of-life measurement (EQ-5D-5L) at 3 and 12 months and daily dyspnea scores after extubation until ICU discharge. The trial is led by Radboud University Medical Center and is conducted at participating Dutch ICUs.

Who should consider this trial

Good fit: Adults aged 18 or older who have been invasively ventilated for more than 48 hours and have failed at least one spontaneous breathing trial (women under 60 must have a negative pregnancy test).

Not a fit: Patients with pre-existing neuromuscular disease, primary neurological reasons for intubation, or contraindications to levosimendan (severe renal or liver failure, prolonged QTc, pregnancy/breastfeeding, known hypersensitivity) are unlikely to benefit or be eligible.

Why it matters

Potential benefit: If successful, the treatment could reduce time on mechanical ventilation, shorten ICU stays, and lower complications related to prolonged ventilation.

How similar studies have performed: Small physiological and pilot studies have suggested levosimendan can improve diaphragm contractility, but large randomized trials in difficult-to-wean ICU patients are limited.

Eligibility criteria

Inclusion Criteria:

* 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 Criteria:

* 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.

Where this trial is running

Arnhem, Gelderland and 7 other locations

• Rijnstate Ziekenhuis Stichting — Arnhem, Gelderland, Netherlands (Recruiting)
• Intensive Care Medicine, Radboud University — Nijmegen, Gelderland, Netherlands (Recruiting)
• Canisius Wilhelmina Ziekenhuis — Nijmegen, Gelderland, Netherlands (Recruiting)
• Jeroen Bosch Ziekenhuis Stichting — 's-Hertogenbosch, North Brabant, Netherlands (Recruiting)
• Catharina Ziekenhuis Stichting — Eindhoven, North Brabant, Netherlands (Not_yet_recruiting)
• Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC) — Rotterdam, South Holland, Netherlands (Not_yet_recruiting)
• Sint Franciscus Vlietland Groep Stichting — Rotterdam, South Holland, Netherlands (Recruiting)
• Maasstad Ziekenhuis Stichting — Rotterdam, South Holland, Netherlands (Recruiting)

Study contacts

• Study coordinator: Esther de Leijer, MD

Conditions Mechanical Ventilation; Weaning Failure; mechanical ventilation; weaning; critically ill patients; levosimendan; diaphragm