Shorter Weaning From Invasive Ventilation With Levosimendan: a Randomized, Double-blind, Multicentre Study in Critically Ill Patients
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 250
- 试验地点
- 11
- 主要终点
- 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.
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Intervention group
Participants randomized to this arm will receive intravenous levosimendan. This group will consist of 125 patients.
干预措施: levosimendan (Drug)
Intervention group
Participants randomized to this arm will receive intravenous levosimendan. This group will consist of 125 patients.
干预措施: Standard care (Other)
Control group
Participants randomized to this arm will receive a placebo consisting of Soluvit. This group will consist of 125 participants.
干预措施: Soluvit (Drug)
Control group
Participants randomized to this arm will receive a placebo consisting of Soluvit. This group will consist of 125 participants.
干预措施: Standard care (Other)
结局指标
主要结局
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.
时间窗: From randomization up until day 28.
In case of death, the subject will be assigned a value of 0 VFD. Day 0 will be defined as the day of randomization.
次要结局
- 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 90.)
- Dyspnea sensation(From extubation up until day 28 or ICU discharge whichever comes first.)
- Quality of life at baseline and at follow up after 3 and 12 months.(From randomization up until 3 and 12 months.)
- The number of patients with a reintubation (for endotracheally intubated patients) or reinstitution of invasive ventilation (for tracheostomized patients) within 7 days after liberation.(From randomization up until day 90.)
- ICU readmission within 90 days.(From randomization up until day 90.)
- The number of days with non-invasive respiratory support (high flow nasal canula or non-invasive ventilation).(From randomization up until day 28.)
- The length of stay in the ICU.(From randomization up until day 90.)
- The length of stay in the hospital.(From randomization up until day 90.)
- Plasma concentration of levosimendan(From 24 hours after start of the first dose of medication up until 120 hours after start of the fist dose of medication.)
- Incidence of clinically significant blood pressure change(From randomization until day 28 or ICU discharge whichever comes first.)
- Incidence of clinically significant heart rate change(From randomization until day 28 or ICU discharge whichever comes first.)
- Vasopressor and inotropic durg use during ICU stay(From randomization until ICU discharge or day 28 whichever comes first.)
- Incidence and type of cardiac dysrhythmia detected by continuous ECG monitoring(From start of infusion up to 30 hours after initiation)
- Daily fluid balance(From randomization up until day 28 or discharge on the ICU, whichever comes first.)
- ICU mortality(From randomization up until day 28.)