Shorter weaning from invasive ventilation with levosimendan: a randomized, double-blind, multicenter study in critically ill patients.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Radboud universitair medisch centrum Stichting

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

17 Sep 2025 → ongoing

Decision date (initial)

2025-05-13

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

ZonMW

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

The number of ventilator free days from randomization up until day 28.

Secondary objectives 3

1. To assess the effect of levosimendan on patient reported outcome.
2. To assess the effect of levosimendan on health care consumption and such increases finite intensive care capacity.
3. To assess pharmacokinetics of levosimendan in critical ill patients.

Conditions and MedDRA coding

Failure to wean from invasive ventilation.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Invasively ventilated for more than 48 hours.
2. Failing at least one spontaneous breathing trial (SBT).
3. Age above 18 years.
4. Female patients of childbearing potential must have a negative pregnancy test (blood or urine) prior to participation
5. 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 7

1. Pre-existing neuromuscular disease (congenital or acquired)
2. 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.
3. 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.
4. Treatment limitation decision in place: do not reintubate
5. Previous treatment with levosimendan within 30 days.
6. Currently in another interventional trial that might interact with study drug or primary outcome.
7. Treatment with intermittent haemodialysis

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The number of ventilator-free days (VFD) from randomization up until day 28.

Secondary endpoints 12

1. The number of ventilator-free days from randomization up day 90.
2. The number of days from randomization to successful weaning from invasive mechanical ventilation.
3. ICU mortality; Mortality at 28 days and 90 days post randomization.
4. Safety endpoints: hypotension, cardiac dysrhythmia (atrial fibrillation, ventricular arrythmias), change in dose of vasopressors after randomization, change in fluid balance after randomization.
5. Dyspnea sensation. Dyspnea will be assessed daily at the end of the spontaneous breathing trial using the Visual Analogue Scale (VAS).
6. EQ-5D-5L scores at baseline and at follow up after 3 and 12 months.
7. 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..
8. ICU readmission within 90 days.
9. The number of days with non-invasive respiratory support (high flow nasal canula or non-invasive ventilation) < 28 days after randomization.
10. The length of stay in the ICU.
11. Levosimendan and its metabolite pharmacokinetics assessed for up to 7 days.
12. The length of stay in the hospital.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Radboud universitair medisch centrum Stichting

Sponsor organisation

Radboud universitair medisch centrum Stichting

Address

Geert Grooteplein Zuid 10

City

Nijmegen

Postcode

6525 GA

Country

Netherlands

Scientific contact point

Organisation

Radboud universitair medisch centrum Stichting

Contact name

Esther de Leijer

Public contact point

Organisation

Radboud universitair medisch centrum Stichting

Contact name

Esther de Leijer

Locations

1 EU/EEA country · 8 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications