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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)

Phase 3
Active, not recruiting
Conditions
Sedation
Interventions
Registration Number
NCT05312385
Lead Sponsor
Sedana Medical
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.

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
235
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PropofolPropofolPropofol administered as intravenous infusion
IsofluraneIsofluraneInhaled isoflurane administered via Sedaconda ACD-S
Primary Outcome Measures
NameTimeMethod
Percentage of time adequate sedation depthDuring 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
NameTimeMethod
Other secondary: Compare mortality at 3 months after randomizationUntil 3 months after randomization

To compare the effect of isoflurane vs propofol on mortality at 3 months after randomization

Key Secondary: Compare the use of opioidsDuring 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

Other secondary: Compare time from sedation termination to extubationDuring 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

Key Secondary: Compare the wake up timeEnd of study treatment (EOT)

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 EOT60 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 effortDuring 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 days alive and free of mechanical ventilation through Study Day 30From 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 ICUFrom 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 EOTFrom 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 randomizationUntil 30 days after randomization

To compare the effect of isoflurane vs propofol on mortality at 30 days after randomization

Other secondary: To compare the safety profile of isoflurane vs propofolBaseline 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 isofluraneDuring 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 propofolDuring study treatment up to 48 (±6) hours

Incidence of restraints measured twice daily

Other secondary: Compare mortality at 6 months after randomizationUntil 6 months after randomization

To compare the effect of isoflurane vs propofol on mortality at 6 months after randomization

Trial Locations

Locations (14)

Emory University

🇺🇸

Atlanta, Georgia, United States

The Cleveland Clinic Foundation

🇺🇸

Cleveland, Ohio, United States

University of Virginia

🇺🇸

Charlottesville, Virginia, United States

The Brigham and Women´s Hospital

🇺🇸

Boston, Massachusetts, United States

MD Anderson Cancer Center

🇺🇸

Houston, Texas, United States

Tufts Medical Center

🇺🇸

Boston, Massachusetts, United States

Houston Methodist Hospital

🇺🇸

Houston, Texas, United States

University of Colorado Anschutz Medical Campus

🇺🇸

Aurora, Colorado, United States

University of Texas Southwestern Medical Center

🇺🇸

Dallas, Texas, United States

University of Cincinnati

🇺🇸

Cincinnati, Ohio, United States

Intermountain Health Care Health Services

🇺🇸

Salt Lake City, Utah, United States

Vanderbilt University Medical Center

🇺🇸

Nashville, Tennessee, United States

University of Chicago

🇺🇸

Chicago, Illinois, United States

Mayo Clinic

🇺🇸

Rochester, Minnesota, United States

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