LEVOSIMENDAN for Failure to wean from invasive ventilation

Inclusion criteria

• {"criterion_text":"- Invasively ventilated for more than 48 hours."}
• {"criterion_text":"- Failing at least one spontaneous breathing trial (SBT)."}
• {"criterion_text":"- Age above 18 years."}
• {"criterion_text":"- Female patients of childbearing potential must have a negative pregnancy test (blood or urine) prior to participation"}
• {"criterion_text":"- Post-menopausal females (> 60 years of age or no menses for 12 consecutive months without an alternative medical cause with confirmatory follicle-stimulating hormone (FSH) level of ≥ 40mIU/mL) do not require contraception during the trial."}

Exclusion criteria

• {"criterion_text":"- Pre-existing neuromuscular disease (congenital or acquired)"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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); pregnancy, breast feeding; known hypersensitivity to levosimendan."}
• {"criterion_text":"- Treatment limitation decision in place: do not reintubate"}
• {"criterion_text":"- Previous treatment with levosimendan within 30 days."}
• {"criterion_text":"- Currently in another interventional trial that might interact with study drug or primary outcome."}
• {"criterion_text":"- Treatment with intermittent haemodialysis"}

Primary endpoints

• {"endpoint_text":"- The number of ventilator-free days (VFD) from randomization up until day 28.","definition_or_measurement_approach":"Count of ventilator-free days from randomization through day 28 (as stated: \"The number of ventilator free days from randomization up until day 28.\")"}

Secondary endpoints

• {"endpoint_text":"- The number of ventilator-free days from randomization up day 90.","definition_or_measurement_approach":"Count of ventilator-free days from randomization through day 90."}
• {"endpoint_text":"- The number of days from randomization to successful weaning from invasive mechanical ventilation.","definition_or_measurement_approach":"Days from randomization until successful weaning event."}
• {"endpoint_text":"- ICU mortality; Mortality at 28 days and 90 days post randomization.","definition_or_measurement_approach":"All-cause ICU mortality and all-cause mortality at 28 and 90 days post-randomization."}
• {"endpoint_text":"- Safety endpoints: hypotension, cardiac dysrhythmia (atrial fibrillation, ventricular arrythmias), change in dose of vasopressors after randomization, change in fluid balance after randomization.","definition_or_measurement_approach":"Monitoring and recording of specified safety events (hypotension, arrhythmias) and changes in vasopressor dosing and fluid balance after randomization."}
• {"endpoint_text":"- Dyspnea sensation. Dyspnea will be assessed daily at the end of the spontaneous breathing trial using the Visual Analogue Scale (VAS).","definition_or_measurement_approach":"Patient-reported dyspnea assessed daily at end of SBT using Visual Analogue Scale (VAS)."}
• {"endpoint_text":"- EQ-5D-5L scores at baseline and at follow up after 3 and 12 months.","definition_or_measurement_approach":"EQ-5D-5L administered at baseline and at follow-up visits at 3 months and 12 months."}
• {"endpoint_text":"- Reintubation (for endotracheally intubated patients) or reinstitution of invasive ventilation (for tracheostomized patients) within 7 days after liberation. An endotracheal intubation beyond 7 days is not considered a “reintubation” but will be classified as an intubation for new event within 90 days..","definition_or_measurement_approach":"Reintubation/reinstitution within 7 days after liberation counted as reintubation; intubation beyond 7 days classified as new event within 90 days."}
• {"endpoint_text":"- ICU readmission within 90 days.","definition_or_measurement_approach":"Any ICU readmission within 90 days post-randomization."}
• {"endpoint_text":"- The number of days with non-invasive respiratory support (high flow nasal canula or non-invasive ventilation) < 28 days after randomization.","definition_or_measurement_approach":"Count of days receiving non-invasive respiratory support within 28 days after randomization."}
• {"endpoint_text":"- The length of stay in the ICU.","definition_or_measurement_approach":"Duration of ICU admission (days)."}
• {"endpoint_text":"- Levosimendan and its metabolite pharmacokinetics assessed for up to 7 days.","definition_or_measurement_approach":"Pharmacokinetic sampling and analysis of levosimendan and metabolites up to 7 days."}
• {"endpoint_text":"- The length of stay in the hospital.","definition_or_measurement_approach":"Duration of hospital admission (days)."}

Netherlands

Latest Decision Or Authorization Date

21-01-2026

Number Of Sites

8

Number Of Participants

250

Primary sponsor

Full Name

Radboud universitair medisch centrum Stichting

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Netherlands

Third parties

• {"country":"","full_name":"ZonMW","duties_or_roles":"Source of monetary support","organisation_type":""}