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)

NCT05327296 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: SED004
• Study Type: interventional
• Target: 282
• Locations: 1 country
• Sites: 16

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.

Conditions

Sedation

Keywords

sedation; mechanical ventilation; propofol; ICU; isoflurane

Outcome Measures

Primary Outcomes (1)

• 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

  The Target Range is RASS -1 to -4. The Richmond Agitation-Sedation Scale (RASS) is used to measure the level of agitation or sedation in patients, particularly in critical care settings. It is a 10-point scale ranging from -5 to +4: +4 Combative - Violent, immediate danger to staff. +3 Very agitated - Pulls or removes tubes or catheters; aggressive. +2 Agitated - Frequent non-purposeful movement, fights ventilator. +1 Restless - Anxious but movements are not aggressive. 0 Alert and calm. -1 Drowsy - Not fully alert, but has sustained awakening (eye-opening/eye contact) to voice for more than 10 seconds. -2 Light sedation - Briefly awakens with eye contact to voice for less than 10 seconds. -3 Moderate sedation - Movement or eye opening to voice, but no eye contact. -4 Deep sedation - No response to voice, but movement or eye opening to physical stimulation. -5 Unarousable - No response to voice or physical stimulation.

  From start to end of study treatment (up to 48 (±6) hours)

Secondary Outcomes (13)

• Key Secondary: The Effect of Isoflurane vs Propofol on Use of Opioids During the Study Treatment Period

  From 60 minutes prior to Baseline until end of study treatment (60 minutes + up to 48 (±6) hours)

• Key Secondary: The Effect of Isoflurane vs Propofol on the Wake up Time at End of Study Drug Treatment

  Up to 4 hours after stop of study drug treatment (up to 54 (±6) hours)

• Key Secondary: The Effect of Isoflurane vs Propofol on Cognitive Recovery After End of Study Drug Treatment

  At 60 minutes (±10 minutes) after end of study drug treatment (up to 49 (±6) hours)

• Key Secondary: The Effect of Isoflurane vs Propofol on Spontaneous Breathing Effort During the Study Drug Treatment Period

  From start to end of study treatment, up to 48 (±6) hours

• Other Secondary: The Effect of Isoflurane vs Propofol on Time From Sedation Termination to Extubation in Patients for Whom Study Drug is Terminated for Extubation

  From end of study drug treatment to extubation (up to 7 Days after randomization)

Study Arms (2)

Isoflurane

EXPERIMENTAL

Inhaled isoflurane administered via Sedaconda ACD-S

Drug: Isoflurane

Propofol

ACTIVE COMPARATOR

Propofol administered as intravenous infusion

Drug: Propofol

Interventions

Isoflurane DRUG

Inhaled isoflurane administered by Sedaconda ACD-S

Isoflurane

Propofol DRUG

Intravenous infusion of propofol

Propofol

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• Sedana Medical: lead

Study Sites (16)

Memorial Health Services

Long Beach, California, 90807, United States

Location

University of California, Los Angeles

Los Angeles, California, 90095, United States

Location

Stanford University

Redwood City, California, 94063, United States

Location

University of California, San Diego

San Diego, California, 92023, United States

Location

University of Miami

Coral Gables, Florida, 33146, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

The Cooper Health System

Camden, New Jersey, 08103, United States

Location

The New York and Presbyterian Hospital

New York, New York, 10032, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Memorial Hermann Health Services

Houston, Texas, 77030, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23284, United States

Location

Related Publications (16)

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• Chanques G, Constantin JM, Devlin JW, Ely EW, Fraser GL, Gelinas C, Girard TD, Guerin C, Jabaudon M, Jaber S, Mehta S, Langer T, Murray MJ, Pandharipande P, Patel B, Payen JF, Puntillo K, Rochwerg B, Shehabi Y, Strom T, Olsen HT, Kress JP. Analgesia and sedation in patients with ARDS. Intensive Care Med. 2020 Dec;46(12):2342-2356. doi: 10.1007/s00134-020-06307-9. Epub 2020 Nov 10.

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• Hughes CG, Mailloux PT, Devlin JW, Swan JT, Sanders RD, Anzueto A, Jackson JC, Hoskins AS, Pun BT, Orun OM, Raman R, Stollings JL, Kiehl AL, Duprey MS, Bui LN, O'Neal HR Jr, Snyder A, Gropper MA, Guntupalli KK, Stashenko GJ, Patel MB, Brummel NE, Girard TD, Dittus RS, Bernard GR, Ely EW, Pandharipande PP; MENDS2 Study Investigators. Dexmedetomidine or Propofol for Sedation in Mechanically Ventilated Adults with Sepsis. N Engl J Med. 2021 Apr 15;384(15):1424-1436. doi: 10.1056/NEJMoa2024922. Epub 2021 Feb 2.

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Related Links

• 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.

MeSH Terms

Interventions

Isoflurane; Propofol

Intervention Hierarchy (Ancestors)

Methyl Ethers; Ethers; Organic Chemicals; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Results Point of Contact

• Title: Director Clinical Development and Operations
• Organization: Sedana Medical

medinfo@sedanamedical.com

+46 (0)8 124 05 200

Study Officials

• Jeremy Beitler, M.D.

  Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 5, 2022
• First Posted: April 14, 2022
• Study Start: June 30, 2022
• Primary Completion: May 28, 2024
• Study Completion: November 14, 2024
• Last Updated: March 24, 2026
• Results First Posted: March 3, 2026

Record last verified: 2026-03

Locations

US (16)