Shorter Weaning From Invasive Ventilation With Levosimendan

NCT ID: NCT07105202

Last Updated: 2026-01-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE4

Total Enrollment

250 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-09-17

Study Completion Date

2028-08-01

Brief Summary

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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.

Detailed Description

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Objective: To assess the effect of levosimendan on the number of ventilator-free days up until day 28.

Study design: WEANLESS is an investigator-initiated, multicenter, double blind, randomized clinical superiority trial in ventilated adult patients admitted to the ICUs of participating hospitals.

Study population: This study will include 250 patients who are invasively ventilated for more than 48 hours and failed at least one SBT. Patients are enrolled from participating ICUs and randomized within 24 hours after failing their first SBT.

Intervention:

Patients will be randomly assigned in a double-blind manner to receive either levosimendan or placebo. The study medication will be administered as a continuous intravenous infusion over 24 hours, starting at a dose of 0.1 µg/kg/min, with the option to increase to 0.2 µg/kg/min after 4 hours if well tolerated. If weaning is not successful after 7 days, a maximum of four treatment cycles may be given. All patients will continue to receive standard ICU care, including daily assessments of readiness to wean from mechanical ventilation.

In addition to the intervention, health-related quality of life will be assessed using the EQ-5D-5L questionnaire at baseline, 3 months, and 12 months after inclusion. Dyspnea scores will be recorded daily after extubation until ICU discharge.

Main study parameters/endpoints: 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. Secondary outcomes include ventilator-free days at day 90, dyspnea scores, reintubation rates, ICU readmission, ICU length of stay, hospital length of stay and mortality. Safety outcomes include the occurrence of cardiac arrhythmias, changes in vasopressor requirements and other adverse events related to levosimendan.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The burden for participants is minimal. Levosimendan is a registered drug with a known safety profile and is already used in critical care settings. The placebo is an infusion with Soluvit. All other care follows standard ICU procedures. Data will be collected from the electronic medical record and routine monitoring. No additional invasive procedures are required solely for the main study.

Conditions

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Mechanical Ventilation Weaning Failure

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Intervention group

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

Group Type ACTIVE_COMPARATOR

levosimendan

Intervention Type 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.

Standard care

Intervention Type OTHER

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

Control group

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

Group Type PLACEBO_COMPARATOR

Soluvit

Intervention Type 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.

Standard care

Intervention Type OTHER

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

Interventions

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levosimendan

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 Type DRUG

Soluvit

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.

Intervention Type DRUG

Standard care

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

Intervention Type OTHER

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Radboud University Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Rijnstate Ziekenhuis Stichting

Arnhem, Gelderland, Netherlands

Site Status RECRUITING

Intensive Care Medicine, Radboud University

Nijmegen, Gelderland, Netherlands

Site Status RECRUITING

Canisius Wilhelmina Ziekenhuis

Nijmegen, Gelderland, Netherlands

Site Status RECRUITING

Jeroen Bosch Ziekenhuis Stichting

's-Hertogenbosch, North Brabant, Netherlands

Site Status RECRUITING

Catharina Ziekenhuis Stichting

Eindhoven, North Brabant, Netherlands

Site Status NOT_YET_RECRUITING

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Rotterdam, South Holland, Netherlands

Site Status NOT_YET_RECRUITING

Sint Franciscus Vlietland Groep Stichting

Rotterdam, South Holland, Netherlands

Site Status RECRUITING

Maasstad Ziekenhuis Stichting

Rotterdam, South Holland, Netherlands

Site Status RECRUITING

Countries

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Netherlands

Central Contacts

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Esther de Leijer, MD

Role: CONTACT

+31243668420

Leo Heunks, MD, PhD

Role: CONTACT

Facility Contacts

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Aart Strang, Mr.

Role: primary

+31880056969

Esther de Leijer, MD

Role: primary

+31243668420

Oscar Hoiting, Dr.

Role: primary

+31243657560

Koen Simons, Dr.

Role: primary

+31735532447

Ashley de Bie, Dr.

Role: primary

+31402399500

Annemijn Jonkman, Dr.

Role: primary

+31107035142

Evert-Jan Wils

Role: primary

+31104616161

Corstiaan den Uil, Mr.

Role: primary

+31102913088

Other Identifiers

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2024-518810-23-00

Identifier Type: CTIS

Identifier Source: secondary_id

2024-518810-23-00

Identifier Type: -

Identifier Source: org_study_id

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