Inhaled Sedation in Critically Ill Patients: a Multicentre Randomized Clinical Trial
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 620
- 试验地点
- 44
- 主要终点
- Ventilator-free days at day 28 from randomization
研究概览
简要总结
The proposal of this study is to compare inhaled sedation with isoflurane administered via the Sedaconda ACD-S system with intravenous sedation with propofol. Patients will be randomized 1:1 to receive either inhaled sedation with isoflurane administered via the Sedaconda ACD device (Sedana Medical, Uppsala, Sweden) or intravenous propofol. The primary endpoint is the number of ventilator-free days at 28 days after randomization.
详细描述
Justification: Isoflurane has recently emerged as an attractive alternative for intensive care unit (ICU) sedation. Due to their favorable pharmaco-kinetic and dynamic profile, this agent has been progressively introduced into clinical practice. Isoflurane has proven to be non-inferior to propofol in terms of efficacy and safety and it has been suggested that it may facilitate ventilator weaning. However, no differences in length of mechanical ventilation were found. These studies have focused on short sedation durations. In fact, long-term effects and outcomes associated with isoflurane for ICU sedation are not yet fully understood.
Hypothesis
Inhaled sedation with isoflurane administered via the Sedaconda ACD-S system in critically ill patients leads to a shorter duration of mechanical ventilation at 28 days and a reduced length of ICU stay compared to intravenous sedation with propofol.
Main objective: To compare the number of ventilator-free days at day 28 post-randomization between critically ill patients receiving sedation with isoflurane versus those receiving intravenous sedation with propofol in critically ill patients expected to require more than 48 hours of invasive mechanical ventilation. Key secondary objective: To compare the number of ICU-free days at day 28 post-randomization in both treatment arms. Secondary objectives: To compare time to extubation after sedation withdrawal, efficacy in maintaining a target level of sedation, compare the percentage of patients requiring one or more additional hypnotics, compare the incidence and duration of delirium at day 28, assess mental, cognitive, and quality of life status at 90 days post-hospital discharge between both treatment groups.
Methodology: Phase IV, low-intervention, open-label, multicenter, randomized controlled trial with intention-to-treat analysis including mechanically ventilated patients expected to require a minimum of 48 hours of mechanical ventilation with a RASS score between -3 and -5. Patients will be randomized 1:1 to receive inhaled sedation with isoflurane administered via the Sedaconda ACD device (Sedana Medical, Uppsala, Sweden) or intravenous sedation with propofol. A total of 620 patients will be included from a pool of 22 participating centers.
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
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •- Adult patients receiving mechanical ventilation, with an anticipated duration >48 hours after randomization, and requiring deep sedation (target RASS between -3 and -5).
排除标准
- •Contraindication to isoflurane or propofol
- •Patients with maternal ancestry from Venezuela, due to the potential presence of an mt-ND4 gene mutation associated with neurological injury after exposure to certain volatile anaesthetic agents
- •Significant air leak, defined as a leak exceeding 30% of the delivered minute ventilation
- •Allergy to isoflurane or propofol
- •Cardiopulmonary arrest
- •History of ventricular tachycardia or long QT syndrome
- •Tidal volume < 300 mL or PaCO₂ > 50 mmHg at the time of randomization.
- •Invasive mechanical ventilation for more than 48 hours at the time of randomization.
- •Pregnancy
- •Breast feeding
- •Acute neurological condition
- •Patients expected to require repeated surgical interventions during their ICU stay.
- •Active humidification strictly required
- •Neuromuscular disease or high spinal cord injury likely to prevent discontinuation of mechanical ventilation due to baseline condition
- •Requirement for benzodiazepine use for a specific indication
- •Life expectancy less than 48 hours, or patients with such a level of severity that death during the ICU stay is considered highly likely.
- •Any condition (e.g., blindness, deafness, dementia) or language barrier that prevents the administration of delirium or cognitive assessment scales.
- •Lack of informed consent
研究组 & 干预措施
Control group
Intravenous sedation with propofol (20 mg/mL). Initial dose: 0.5-1 mg/kg/h. Gradual dose increase until target RASS is achieved. Do not exceed 4 mg/kg/h. If the target RASS is not achieved at the maximum dose, a second hypnotic agent may be added.
干预措施: Propofol (Drug)
Study group
Inhaled sedation with Isoflurane. Initial dose: 3 mL/h. Gradual dose increase until target RASS is achieved. Do not exceed 14 mL/h. Guided by end tidal isoflurane concentration (EtISO), the recommended maximum dose for prolonged use is 1%. Short periods at up to 1.5% may be considered. If the target RASS is not achieved at the maximum dose, a second hypnotic agent may be added.
干预措施: Isoflurane (Drug)
结局指标
主要结局
Ventilator-free days at day 28 from randomization
时间窗: From randomization until day 28
Number of days between randomization and day 28 during which the patient is alive and free from invasive mechanical ventilation. Patients who die before day 28, or who remain on mechanical ventilation at day 28, are assigned zero ventilator-free days.
Ventilator-free days at day 28 from randomization
时间窗: From randomization until day 28
Number of days between randomization and day 28 during which the patient is alive and free from invasive mechanical ventilation. Patients who die before day 28, or who remain on mechanical ventilation at day 28, are assigned zero ventilator-free days.
次要结局
- Number of Participants With Psychological disorders(at 90 days of hospital discharge)
- Number of Participants With Treatment-Related Adverse Events(From randomization to day 28)
- Key secondary objective: ICU-free days at day 28 post-randomization(From randomization until day 28)
- Time to extubation(From randomization until day 28)
- Number of Participants With Delirium(From randomization until extubation or day 28)
- Key secondary objective: ICU-free days at day 28 post-randomization(From randomization until day 28)
- Time to extubation(From randomization until day 28)
- Administration of rescue sedation(From randomization until day 28)
- Sedation efficacy(From randomization until extubation or day 28)
- Number of Participants With Delirium(From randomization until extubation or day 28)
- Mortality(From randomization to day 60)
- Number of Participants With Psychological disorders(at 90 days of hospital discharge)
- Number of Participants With Cognitive Disorders(at 90 days of hospital discharge)
- Number of Participants With Treatment-Related Adverse Events(From randomization to day 28)
研究者
José Manuel Añón
Head of Department of Critical Care Medicine
Instituto de Investigación Hospital Universitario La Paz