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-ICU2)

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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-ICU2)

Conditions
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Sedation

Intervention / Treatment
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* Drug: Isoflurane
* Drug: Propofol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Isoflurane<br>Inhaled isoflurane administered via Sedaconda ACD-S | Drug: Isoflurane<br>* Inhaled isoflurane administered by Sedaconda ACD-S<br>|
| Active Comparator: Propofol<br>Propofol administered as intravenous infusion | Drug: Propofol<br>* Intravenous infusion of propofol<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of time adequate sedation depth | To compare 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 | During study treatment up to 48 (±6) hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Key Secondary: Compare the use of opioids | To compare the effect of isoflurane vs propofol on use of opioids during the study drug treatment period measuring CPOT | During study treatment up to 48 (±6) hours | 
| Key Secondary: Compare the wake up time | To compare the effect of isoflurane vs propofol on the wake up time at end of study drug treatment | Time from stop of study drug treatment up to 4 hours | 
| Key Secondary: Compare the cognitive recovery after EOT | To compare the effect of isoflurane vs propofol on cognitive recovery after EOT by measuring CAM-ICU-7 | 60 minutes after EOT | 
| Key Secondary: Compare the spontaneous breathing effort | To compare the effect of isoflurane vs propofol on spontaneous breathing effort during the study drug treatment period by measuring • Airway occlusion pressure, pressure support or if observed respiratory rate exceeds set respiratory rate | During study treatment up to 48 (±6) hours | 
| Other secondary: Compare time from sedation termination to extubation | To compare the effect of isoflurane vs propofol on time from sedation termination to extubation in patients for whom study drug is terminated for extubation | During study treatment | 
| Other secondary: Compare days alive and free of mechanical ventilation through Study Day 30 | To compare 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: Compare days alive and free of the ICU | To compare 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: Compare delirium and coma free days until 7 days after EOT | To compare the effect of isoflurane vs propofol on delirium and coma free days until 7 days after EOT | From start of study treatment until 7 days after EOT | 
| Other secondary: Compare mortality at 30 days after randomization | To compare the effect of isoflurane vs propofol on mortality at 30 days after randomization | Until 30 days after randomization | 
| Other secondary: Compare mortality at 3 months after randomization | To compare the effect of isoflurane vs propofol on mortality at 3 months after randomization | Until 3 months after randomization | 
| Other secondary: Compare mortality at 6 months after randomization | To compare the effect of isoflurane vs propofol on mortality at 6 months after randomization | Until 6 months after randomization | 
| Other secondary: To compare the safety profile of isoflurane vs propofol | To compare the safety profile of isoflurane vs propofol in respect to reported Adverse Event | Baseline to end of study treatment, safety lab from baseline up to 48hrs post treatment, AEs from start study treatment up to day 30 | 
| Other secondary: To assess Sedaconda ACD-S device deficiencies in patients receiving isoflurane | To assess Sedaconda ACD-S device deficiencies in patients receiving isoflurane by Sedaconda ACD-S by reported Adverse Event | During study treatment up to 48 (±6) hours | 
| Other secondary: To compare the use of restraints in patients receiving isoflurane vs propofol | Incidence of restraints measured twice daily | During study treatment up to 48 (±6) hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sedation, mechanical ventilation, propofol, ICU, isoflurane