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) (INSPiRE-ICU2)

• ClinicalTrials.gov Identifier: NCT05327296
• Recruitment Status: Recruiting
• First Posted: April 14, 2022
• Last Update Posted: March 20, 2024
• Sponsor: Sedana Medical
• Information provided by (Responsible Party): Sedana Medical

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 (Clinical Trial)
• Estimated 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: June 30, 2022
• Estimated Primary Completion Date: June 30, 2024
• Estimated Study Completion Date: December 30, 2024

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

Outcome Measures

Primary Outcome Measures :

1. Percentage of time adequate sedation depth [ Time Frame: 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 :

1. Key Secondary: Compare the use of opioids [ Time Frame: 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
2. Key Secondary: Compare the wake up time [ Time Frame: 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
3. Key Secondary: Compare the cognitive recovery after EOT [ Time Frame: 60 minutes after EOT ]
   To compare the effect of isoflurane vs propofol on cognitive recovery after EOT by measuring CAM-ICU-7
4. Key Secondary: Compare the spontaneous breathing effort [ Time Frame: 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

5. Other secondary: Compare time from sedation termination to extubation [ Time Frame: 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
6. Other secondary: Compare days alive and free of mechanical ventilation through Study Day 30 [ Time Frame: 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
7. Other secondary: Compare days alive and free of the ICU [ Time Frame: 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
8. Other secondary: Compare delirium and coma free days until 7 days after EOT [ Time Frame: 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
9. Other secondary: Compare mortality at 30 days after randomization [ Time Frame: Until 30 days after randomization ]
   To compare the effect of isoflurane vs propofol on mortality at 30 days after randomization
10. Other secondary: Compare mortality at 3 months after randomization [ Time Frame: Until 3 months after randomization ]
    To compare the effect of isoflurane vs propofol on mortality at 3 months after randomization
11. Other secondary: Compare mortality at 6 months after randomization [ Time Frame: Until 6 months after randomization ]
    To compare the effect of isoflurane vs propofol on mortality at 6 months after randomization
12. Other secondary: To compare the safety profile of isoflurane vs propofol [ Time Frame: 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
13. Other secondary: To assess Sedaconda ACD-S device deficiencies in patients receiving isoflurane [ Time Frame: 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
14. Other secondary: To compare the use of restraints in patients receiving isoflurane vs propofol [ Time Frame: During study treatment up to 48 (±6) hours ]
    Incidence of restraints measured twice daily

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Contacts

Contact: Magnus Falkenhav, M.D.; +46 70 856 1687; magnus.falkenhav@sedanamedical.com

Locations

United States, California

Memorial Health Services; Recruiting

Long Beach, California, United States, 90807

University of California, Los Angeles; Recruiting

Los Angeles, California, United States, 90095

Stanford University; Recruiting

Redwood City, California, United States, 94063

University of California, San Diego; Recruiting

San Diego, California, United States, 92023

United States, Florida

University of Miami; Recruiting

Coral Gables, Florida, United States, 33146

United States, Illinois

Rush University Medical Center; Recruiting

Chicago, Illinois, United States, 60612

United States, Massachusetts

Massachusetts General Hospital; Recruiting

Boston, Massachusetts, United States, 02114

Beth Israel Deaconess Medical Center; Recruiting

Boston, Massachusetts, United States, 02215

United States, Michigan

University of Michigan; Recruiting

Ann Arbor, Michigan, United States, 48109

Henry Ford Health System; Recruiting

Detroit, Michigan, United States, 48202

United States, New Jersey

The Cooper Health System; Not yet recruiting

Camden, New Jersey, United States, 08103

United States, New York

The New York and Presbyterian Hospital; Recruiting

New York, New York, United States, 10032

United States, Ohio

Ohio State University; Recruiting

Columbus, Ohio, United States, 43210

United States, Pennsylvania

Thomas Jefferson University; Recruiting

Philadelphia, Pennsylvania, United States, 19107

United States, Texas

Memorial Hermann Health Services; Recruiting

Houston, Texas, United States, 77030

United States, Virginia

Virginia Commonwealth University; Recruiting

Richmond, Virginia, United States, 23284

Sponsors and Collaborators

Sedana Medical

Investigators

• Principal Investigator: Jeremy Beitler, M.D.; Columbia University

More Information

Additional Information:

Isoflurane 100% inhalation vapour, liquid. Summary of product characteristics. West Drayton, United Kingdon. Piramal Critical Care Ltd. Electronic medicines compendium(emc), last updated 29 October 2019. Accessed 09 September 2020. 

Publications:

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• Responsible Party: Sedana Medical
• ClinicalTrials.gov Identifier: NCT05327296
• Other Study ID Numbers: SED004
• First Posted: April 14, 2022
• Last Update Posted: March 20, 2024
• Last Verified: March 2024

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Sedana Medical:

sedation; mechanical ventilation; propofol; ICU; isoflurane

Additional relevant MeSH terms:

Propofol; Isoflurane; Hypnotics and Sedatives; Central Nervous System Depressants; Physiological Effects of Drugs; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Anesthetics, Inhalation