Shorter Weaning From Invasive Ventilation With Levosimendan

NCT07105202 | Recruiting Phase 4 DMC

• 1 other identifier: 2024-518810-23-00
• Study Type: interventional
• Target: 250
• Locations: 1 country
• Sites: 8

Brief 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.

Conditions

Weaning Failure; Mechanical Ventilation

Keywords

mechanical ventilation; weaning; critically ill patients; levosimendan; diaphragm

Outcome Measures

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.

  From randomization up until day 28.

Secondary Outcomes (17)

• The number of ventilator-free days from randomization up until day 90.

  From randomization up until day 90.

• The number of days from randomization to successful weaning from invasive ventilation.

  From randomization up until day 90.

• ICU mortality

  From randomization up until day 28.

• ICU mortality

  From randomization up until day 90.

• Dyspnea sensation

  From extubation up until day 28 or ICU discharge whichever comes first.

Study Arms (2)

Intervention group

ACTIVE COMPARATOR

Participants randomized to this arm will receive intravenous levosimendan. This group will consist of 125 patients.

Drug: levosimendan; Other: Standard care

Control group

PLACEBO COMPARATOR

Participants randomized to this arm will receive a placebo consisting of Soluvit. This group will consist of 125 participants.

Drug: Soluvit; Other: Standard care

Interventions

Soluvit DRUG

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.

Control group

Standard care OTHER

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

Control group; Intervention group

levosimendan DRUG

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.

Intervention group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Radboud University Medical Center: lead

Study Sites (8)

Rijnstate Ziekenhuis Stichting

Arnhem, Gelderland, 6815AD, Netherlands

RECRUITING

Intensive Care Medicine, Radboud University

Nijmegen, Gelderland, 6500 HB, Netherlands

RECRUITING

Canisius Wilhelmina Ziekenhuis

Nijmegen, Gelderland, 6532SZ, Netherlands

RECRUITING

Jeroen Bosch Ziekenhuis Stichting

's-Hertogenbosch, North Brabant, 5223GZ, Netherlands

RECRUITING

Catharina Ziekenhuis Stichting

Eindhoven, North Brabant, 5623EJ, Netherlands

NOT YET RECRUITING

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Rotterdam, South Holland, 3015GD, Netherlands

NOT YET RECRUITING

Sint Franciscus Vlietland Groep Stichting

Rotterdam, South Holland, 3045 PM, Netherlands

RECRUITING

Maasstad Ziekenhuis Stichting

Rotterdam, South Holland, 3079DZ, Netherlands

RECRUITING

MeSH Terms

Interventions

Simendan; Standard of Care

Intervention Hierarchy (Ancestors)

Hydrazones; Hydrazines; Organic Chemicals; Pyridazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Central Study Contacts

Esther de Leijer, MD

CONTACT

+31243668420; esther.deleijer@radboudumc.nl

Leo Heunks, MD, PhD

CONTACT

leo.heunks@radboudumc.nl

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 9, 2025
• First Posted: August 5, 2025
• Study Start: September 17, 2025
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2028
• Last Updated: January 9, 2026

Record last verified: 2025-05

Locations

NL (8)