Clinical trial NCT05312385: 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)
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-ICU1)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Sedation
Keywords: sedation
mechanical ventilation
isoflurane
propofol
ICU
Lead sponsor: Sedana Medical
Sponsor class: INDUSTRY
First posted: 2022-04-05
Enrollment: 235
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of time adequate sedation depth
timeFrame: During study treatment up to 48 (±6) hours
Secondary outcomes:
measure: Key Secondary: Compare the use of opioids
timeFrame: During study treatment up to 48 (±6) hours
measure: Key Secondary: Compare the wake up time
timeFrame: End of study treatment (EOT)
measure: Key Secondary: Compare the cognitive recovery after EOT
timeFrame: 60 minutes after EOT
measure: Key Secondary: Compare the spontaneous breathing effort
timeFrame: During study treatment up to 48 (±6) hours
measure: Other secondary: Compare time from sedation termination to extubation
timeFrame: During study treatment
measure: Other secondary: Compare days alive and free of mechanical ventilation through Study Day 30
timeFrame: From start of study treatment up to 30 days
measure: Other secondary: Compare days alive and free of the ICU
timeFrame: From start of study treatment up to 30 days
measure: Other secondary: Compare delirium and coma free days until 7 days after EOT
timeFrame: From start of study treatment until 7 days after EOT
measure: Other secondary: Compare mortality at 30 days after randomization
timeFrame: Until 30 days after randomization
measure: Other secondary: Compare mortality at 3 months after randomization
timeFrame: Until 3 months after randomization
measure: Other secondary: Compare mortality at 6 months after randomization
timeFrame: Until 6 months after randomization
measure: Other secondary: To compare the safety profile of isoflurane vs propofol
timeFrame: Baseline to end of study treatment, safety lab from baseline up to 48hrs post treatment, AEs from start study treatment up to day 30
measure: Other secondary: To assess Sedaconda ACD-S device deficiencies in patients receiving isoflurane
timeFrame: During study treatment up to 48 (±6) hours
measure: Other secondary: To compare the use of restraints in patients receiving isoflurane vs propofol
timeFrame: During study treatment up to 48 (±6) hours
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado Anschutz Medical Campus
state: Colorado
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Boston
country: United States
facility: The Brigham and Women´s Hospital
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: The Cleveland Clinic Foundation
state: Ohio
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: Intermountain Health Care Health Services
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
Study officials:
affiliation: Vanderbilt University Medical Center
name: Kimberly Rengel, M.D.
role: PRINCIPAL_INVESTIGATOR
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