A Phase 3, Multicenter, Randomized, Controlled, Open Label, Assessor-Blinded Study to Evaluate the Efficacy and Safety of Inhaled Isoflurane Delivered Via the Sedaconda ACD-S Compared to Intravenous Propofol for Sedation of Mechanically Ventilated Intensive Care Unit Adult Patients (INSPiRE-ICU1)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 277
- 试验地点
- 14
- 主要终点
- The Percentage of Time Sedation Depth is Maintained Within the Target Range, in Absence of Rescue Sedation, as Assessed According to the RASS Scale, in Isoflurane- vs Propofol-treated Patients
研究概览
简要总结
This is a study to compare safety and efficacy of inhaled isoflurane administered via the Sedaconda ACD-S device system versus intravenous propofol for sedation of mechanically ventilated patients in the Intensive Care Unit (ICU) setting.
详细描述
This is a phase 3, multicenter, randomized, controlled, open-label, assessor-blinded study to evaluate the efficacy and safety of inhaled isoflurane delivered via the Sedaconda ACD-S compared to intravenous propofol for sedation of mechanically ventilated Intensive Care Unit (ICU) adult patients.
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)
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
- •Adults ≥18 years of age;
- •Patients who are anticipated to require >12 hours of invasive mechanical ventilation and continuous sedation in the ICU; and
- •Receipt of continuous sedation due to clinical need for sedation to RASS <0.
排除标准
- •Need for RASS -5;
- •Sedation for invasive mechanical ventilation immediately prior to Baseline for >72 hours;
- •Severe neurological condition before ICU admission that causes the patient to lack ability to participate in the study (ie, unable to be assessed for RASS and CPOT);
- •Ventilator tidal volume <200 or >1000 mL at Baseline;
- •Need for extracorporeal membrane oxygenation (ECMO), extracorporeal CO2 removal (ECCO2R), high frequency oscillation ventilation (HFOV), or high frequency percussive ventilation (HFPV) at Screening;
- •Comfort care only (end of life care);
- •Contraindication to propofol or isoflurane;
- •Known or family history of MH;
- •Severe hemodynamic compromise, defined as the need for norepinephrine ≥0.3 mcg/kg/min (or equivalent vasopressor dose) to maintain blood pressure within acceptable range, assumed to be mean arterial pressure ≥65 mmHg unless prescribed clinically;
- •Allergy to isoflurane or propofol, or have propofol infusion syndrome.
- •History of ventricular tachycardia/Long QT Syndrome;
- •Requirement of IV benzodiazepine or barbiturate administration for seizures or dependencies, including alcohol withdrawal
- •Neuromuscular disease that impairs spontaneous ventilation (eg, C5 or higher spinal cord injury, amyotrophic lateral sclerosis, etc);
- •Concurrent enrollment in another study that, in the Investigator's opinion, would impact the patient's safety or assessments of this study;
- •Participation in other study involving investigational drug(s) or devices(s) within 30 days prior to Randomization;
- •Anticipated requirement of treatment with continuous infusion of a neuromuscular blocking agent for >4 hours;
- •Female patients who are pregnant or breast-feeding;
- •Imperative need for continuous active humidification through mechanical ventilation circuit;
- •Attending physician's refusal to include the patient; or
- •Inability to obtain informed consent.
研究组 & 干预措施
Propofol
Propofol administered as intravenous infusion
干预措施: Propofol (Drug)
Isoflurane
Inhaled isoflurane administered via Sedaconda ACD-S
干预措施: Isoflurane (Drug)
结局指标
主要结局
The Percentage of Time Sedation Depth is Maintained Within the Target Range, in Absence of Rescue Sedation, as Assessed According to the RASS Scale, in Isoflurane- vs Propofol-treated Patients
时间窗: From start to end of study treatment (up to 48 (±6) hours)
The Target Range is RASS -1 to -4. The Richmond Agitation-Sedation Scale (RASS) is used to measure the level of agitation or sedation in patients, particularly in critical care settings. It is a 10-point scale ranging from -5 to +4: +4 Combative - Violent, immediate danger to staff. +3 Very agitated - Pulls or removes tubes or catheters; aggressive. +2 Agitated - Frequent non-purposeful movement, fights ventilator. +1 Restless - Anxious but movements are not aggressive. 0 Alert and calm. -1 Drowsy - Not fully alert, but has sustained awakening (eye-opening/eye contact) to voice for more than 10 seconds. -2 Light sedation - Briefly awakens with eye contact to voice for less than 10 seconds. -3 Moderate sedation - Movement or eye opening to voice, but no eye contact. -4 Deep sedation - No response to voice, but movement or eye opening to physical stimulation. -5 Unarousable - No response to voice or physical stimulation.
次要结局
- Key Secondary: The Effect of Isoflurane vs Propofol on Use of Opioids During the Study Treatment Period(From 60 minutes prior to Baseline until end of study treatment (60 minutes + up to 48 (±6) hours))
- Key Secondary: The Effect of Isoflurane vs Propofol on the Wake up Time at End of Study Drug Treatment(Up to 4 hours after stop of study drug treatment (up to 54 (±6) hours))
- Key Secondary: The Effect of Isoflurane vs Propofol on Cognitive Recovery After End of Study Drug Treatment(At 60 minutes (±10 minutes) after end of study drug treatment (up to 49 (±6) hours))
- Key Secondary: The Effect of Isoflurane vs Propofol on Spontaneous Breathing Effort During the Study Drug Treatment Period(From start to end of study treatment, up to 48 (±6) hours)
- Other Secondary: The Effect of Isoflurane vs Propofol on Time From Sedation Termination to Extubation in Patients for Whom Study Drug is Terminated for Extubation(From end of study treatment sedation to extubation (up to 7 Days after randomization))
- Other Secondary: The Effect of Isoflurane vs Propofol on Days Alive and Free of Mechanical Ventilation Through Study Day 30(From start of study treatment up to 30 days)
- Other Secondary: The Effect of Isoflurane vs Propofol on Days Alive and Free of the ICU(From start of study treatment up to 30 days)
- Other Secondary: The Effect of Isoflurane vs Propofol on Delirium and Coma Free Days Until 7 Days After End of Study Treatment(From start of study treatment until 7 days after end of treatment (up to 9 days post study drug treatment initiation))
- Other Secondary: The Effect of Isoflurane vs Propofol on Mortality at 30 Days After Randomization(At 30 days after randomization)
- Other Secondary: The Effect of Isoflurane vs Propofol on Mortality at 3 Months After Randomization(At 3 months after randomization)
- Other Secondary: The Effect of Isoflurane vs Propofol on Mortality at 6 Months After Randomization(At 6 months after randomization)
- Other Secondary: Sedaconda ACD-S Device Deficiencies in Patients Receiving Isoflurane(From start to end of study treatment (up to 48 (±6) hours))
- Other Secondary: The Use of Restraints in Patients Receiving Isoflurane vs Propofol(From start to end of study treatment (up to 48 (±6) hours))