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)

Sponsor

Sedana Medical (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05327296

Collaborator

(none)

235

Enrollment

Location

Arms

Anticipated Duration (Months)

13.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Sedation	Drug: Isoflurane Drug: Propofol	Phase 3

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

235 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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)

Actual Study Start Date :

Jun 30, 2022

Anticipated Primary Completion Date :

Jun 15, 2023

Anticipated Study Completion Date :

Dec 30, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Isoflurane Inhaled isoflurane administered via Sedaconda ACD-S	Drug: Isoflurane Inhaled isoflurane administered by Sedaconda ACD-S
Active Comparator: Propofol Propofol administered as intravenous infusion	Drug: Propofol Intravenous infusion of propofol

Arm

Intervention/Treatment

Experimental: Isoflurane

Inhaled isoflurane administered via Sedaconda ACD-S

Drug: Isoflurane

Inhaled isoflurane administered by Sedaconda ACD-S

Active Comparator: Propofol

Propofol administered as intravenous infusion

Drug: Propofol

Intravenous infusion of propofol

Outcome Measures

Primary Outcome Measures

Percentage of time adequate sedation depth [During study treatment up to 48 (±6) hours]
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

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.