Sevoflurane for Sedation in Acute Respiratory Distress Syndrome: A Multicenter Prospective Randomized Trial
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 700
- 试验地点
- 34
- 主要终点
- Ventilator-free days through day 28
研究概览
简要总结
This study evaluates whether a sedation with inhaled sevoflurane will decrease mortality and increase time off the ventilator at 28 days in patients with acute respiratory distress syndrome (ARDS).
Half of the patients will receive inhaled sedation with sevoflurane and the other half will receive intravenous sedation with propofol.
详细描述
PRIMARY OBJECTIVE:
To assess the efficacy of a sedation with inhaled sevoflurane in improving in reducing mortality and morbidity in patients with moderate-severe ARDS in comparison to a control group receiving intravenous sedation with propofol.
PRIMARY HYPOTHESIS:
Inhaled sedation with sevoflurane will improve a composite outcome of mortality and time off the ventilator at 28 days, in patients with moderate-severe ARDS.
The trial will accrue a maximum of 700 patients. Patients will be recruited from participating intensive care units and randomized to the active (inhaled sevoflurane) or control (intravenous propofol).
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
- Single (Outcomes Assessor)
盲法说明
At each participating center, patients will be followed up for primary and secondary endpoints by members of the research staff who will be unaware of the trial group allocation. Information on whether the primary and secondary outcomes occur will be collected and entered into the electronic web-based case report form (eCRF) by trial or clinical trained personal (clinical research associate), blinded to the allocation group, under the supervision of the local principal investigator (PI) or designee who will also be unaware of the trial group allocation.
Finally, the independent trial statistician and the members of the data monitoring and safety committee (DMSC) will also remain blinded for the allocation during analysis. However, the observation of differences in serious adverse events between the two groups will allow, for safety reasons may the DMSC deem necessary, to unblind allocation groups.
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
- •Age ≥18 years
- •Presence for ≤24 hours of all of the following conditions, within one week of a clinical insult or new or worsening respiratory symptoms:
- •PaO2/FiO2 <150 mmHg with positive end-expiratory pressure (PEEP) ≥8 cmH2O (or, if arterial blood gas not available, SpO2/FiO2 that is equivalent to a PaO2/FiO2 <150 mmHg with PEEP ≥8 cmH2O and a confirmatory SpO2/FiO2 between 1-6 hours after the initial SpO2/FiO2 determination)
- •Bilateral opacities not fully explained by effusions, lobar/lung collapse, or nodules
- •Respiratory failure not fully explained by cardiac failure or fluid overload; need objective assessment (e.g., echocardiography) to exclude hydrostatic edema if no risk factor present
排除标准
- •Absence of affiliation to the French Sociale security
- •Patient under a tutelage measure or placed under judicial protection
- •Continuous sedation with inhaled sevoflurane at enrollment
- •Known pregnancy
- •Currently receiving ECMO therapy
- •Chronic respiratory failure defined as PaCO2 >60 mmHg in the outpatient setting
- •Home mechanical ventilation (non-invasive ventilation or via tracheotomy) except for CPAP/BIPAP used solely for sleep-disordered breathing
- •Body mass index >40 kg/m2
- •Chronic liver disease defined as a Child-Pugh score of 12-15
- •Expected duration of mechanical ventilation <48 hours
- •Moribund patient, i.e. not expected to survive 24 hours despite intensive care
- •Burns >70% total body surface
- •Previous hypersensitivity or anaphylactic reaction to sevoflurane or cisatracurium
- •Medical history of malignant hyperthermia
- •Long QT syndrome at risk of arrhythmic events
- •Medical history of liver disease attributed to previous exposure to a halogenated agent (including sevoflurane)
- •Known hypersensitivity to propofol or any of its components
- •Known allergy to eggs, egg products, soybeans, and soy products
- •Suspected or proven intracranial hypertension
- •Tidal volume of 6 mL/kg predicted body weight (PBW) below 200 mL (as recommended by the manufacturer for the use of the AnaConDa-S (Sedana Medical, Danderyd, Sweden)
- •Enrollment in another interventional ARDS trial with direct impact on sedation and mechanical ventilation
- •Endotracheal ventilation for greater than 120 hours (5 days)
- •Persistent bronchopleural fistula despite chest tube drainage
- •PaO2/FiO2 (if available) >200 mmHg after meeting inclusion criteria and before randomization
研究组 & 干预措施
intravenous sedation with propofol
intravenous sedation with propofol, as already routinely used in participating ICUs
干预措施: intravenous sedation with propofol (Drug)
inhaled sedation with sevoflurane
Inhaled sedation with sevoflurane, as vaporized via the Anesthesia Conserving Device (AnaConDa-S, Sedana Medical, Danderyd, Sweden)
干预措施: Inhaled sedation with sevoflurane (Drug)
结局指标
主要结局
Ventilator-free days through day 28
时间窗: Day 28
Number of days alive and off the ventilator at 28 days, thereby considering death as a competing event
次要结局
- All-cause, all-location 28-day mortality (Secondary outcome)(Day 28)
- 90-day survival (Key secondary outcome)(Day 90)
- All-cause hospital 28-day mortality (Secondary outcome)(Day 28)
- All-cause, all-location 7-day mortality (Secondary outcome)(Day 7)
- All-cause, all-location 14-day mortality (Secondary outcome)(Day 14)