Shorter Weaning From Invasive Ventilation With Levosimendan
Trial statusRecruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexAll
Age18+
SponsorRadboud University Medical Center
About this trial
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 criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
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.
Trial design
Design model
Parallel
Treatments tested in this trial
levosimendan
DrugParticipants 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.
Soluvit
DrugParticipants 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.
Standard care
Other interventionAll patients in this arm will receive standard ICU care, including daily assessments for readiness to wean from invasive ventilation.
Treatment groups
250 Participants
are divided into 2 treatment groupsGroup A: Intervention groupActive comparator 2 interventions
Group B: Control groupPlacebo comparator 2 interventions
Trial outcomes
Primary outcomes
1
The primary endpoint of the study is the number of ventilator-free days and alive (VFD) at day 28 from randomization. This is a composite endpoint combining both mortality and the duration of ventilation.
In case of death, the subject will be assigned a value of 0 VFD. Day 0 will be defined as the day of randomization.
Time frame
From randomization up until day 28.Secondary outcomes
1
The number of ventilator-free days from randomization up until day 90.
Time frame
From randomization up until day 90.2
The number of days from randomization to successful weaning from invasive ventilation.
Weaning success defined as: for intubated patients extubation without death or reintubation within the next 7 days, or discharge from the ICU without invasive ventilation within 7 days. Whichever comes first. For tracheostomized patients, weaning success is defined as ventilation through tracheostomy without any invasive ventilation during 7 consecutive days, or discharged from the ICU with unassisted breathing, whichever came first.
Time frame
From randomization up until day 90.3
ICU mortality
Time frame
From randomization up until day 28.4
ICU mortality
Time frame
From randomization up until day 90.Sponsors and contacts
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Source ClinicalTrials.gov