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)

NCT05312385 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: SED003
• Study Type: interventional
• Target: 277
• Locations: 1 country
• Sites: 14

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; isoflurane; propofol; ICU

Outcome Measures

Primary Outcomes (1)

• 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

  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 treatment sedation to extubation (up to 7 Days after randomization)

Study Arms (2)

Isoflurane

EXPERIMENTAL

Inhaled isoflurane administered via Sedaconda ACD-S

Drug: Isoflurane; Drug: Isoflurane (run-ins)

Propofol

ACTIVE COMPARATOR

Propofol administered as intravenous infusion

Drug: Propofol

Interventions

Isoflurane (run-ins) DRUG

Inhaled isoflurane administered by Sedaconda ACD-S 3-5 run-in patients were enrolled at each site prior to randomization

Isoflurane

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 (14)

University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

The Brigham and Women´s Hospital

Boston, Massachusetts, 02115, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45219, United States

Location

The Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Intermountain Health Care Health Services

Salt Lake City, Utah, 84111, United States

Location

University of Virginia

Charlottesville, Virginia, 22903, United States

Location

Related Publications (16)

• Devlin JW, Skrobik Y, Gelinas C, Needham DM, Slooter AJC, Pandharipande PP, Watson PL, Weinhouse GL, Nunnally ME, Rochwerg B, Balas MC, van den Boogaard M, Bosma KJ, Brummel NE, Chanques G, Denehy L, Drouot X, Fraser GL, Harris JE, Joffe AM, Kho ME, Kress JP, Lanphere JA, McKinley S, Neufeld KJ, Pisani MA, Payen JF, Pun BT, Puntillo KA, Riker RR, Robinson BRH, Shehabi Y, Szumita PM, Winkelman C, Centofanti JE, Price C, Nikayin S, Misak CJ, Flood PD, Kiedrowski K, Alhazzani W. Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU. Crit Care Med. 2018 Sep;46(9):e825-e873. doi: 10.1097/CCM.0000000000003299.

  PMID: 30113379 BACKGROUND

• Shehabi Y, Howe BD, Bellomo R, Arabi YM, Bailey M, Bass FE, Bin Kadiman S, McArthur CJ, Murray L, Reade MC, Seppelt IM, Takala J, Wise MP, Webb SA; ANZICS Clinical Trials Group and the SPICE III Investigators. Early Sedation with Dexmedetomidine in Critically Ill Patients. N Engl J Med. 2019 Jun 27;380(26):2506-2517. doi: 10.1056/NEJMoa1904710. Epub 2019 May 19.

  PMID: 31112380 BACKGROUND

• Kress JP, Pohlman AS, O'Connor MF, Hall JB. Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation. N Engl J Med. 2000 May 18;342(20):1471-7. doi: 10.1056/NEJM200005183422002.

  PMID: 10816184 BACKGROUND

• Mehta S, Burry L, Cook D, Fergusson D, Steinberg M, Granton J, Herridge M, Ferguson N, Devlin J, Tanios M, Dodek P, Fowler R, Burns K, Jacka M, Olafson K, Skrobik Y, Hebert P, Sabri E, Meade M; SLEAP Investigators; Canadian Critical Care Trials Group. Daily sedation interruption in mechanically ventilated critically ill patients cared for with a sedation protocol: a randomized controlled trial. JAMA. 2012 Nov 21;308(19):1985-92. doi: 10.1001/jama.2012.13872.

  PMID: 23180503 BACKGROUND

• Sackey PV, Martling CR, Carlsward C, Sundin O, Radell PJ. Short- and long-term follow-up of intensive care unit patients after sedation with isoflurane and midazolam--a pilot study. Crit Care Med. 2008 Mar;36(3):801-6. doi: 10.1097/CCM.0B013E3181652FEE.

  PMID: 18431266 BACKGROUND

• Mesnil M, Capdevila X, Bringuier S, Trine PO, Falquet Y, Charbit J, Roustan JP, Chanques G, Jaber S. Long-term sedation in intensive care unit: a randomized comparison between inhaled sevoflurane and intravenous propofol or midazolam. Intensive Care Med. 2011 Jun;37(6):933-41. doi: 10.1007/s00134-011-2187-3. Epub 2011 Mar 29.

  PMID: 21445642 BACKGROUND

• Meiser A, Volk T, Wallenborn J, Guenther U, Becher T, Bracht H, Schwarzkopf K, Knafelj R, Faltlhauser A, Thal SC, Soukup J, Kellner P, Druner M, Vogelsang H, Bellgardt M, Sackey P; Sedaconda study group. Inhaled isoflurane via the anaesthetic conserving device versus propofol for sedation of invasively ventilated patients in intensive care units in Germany and Slovenia: an open-label, phase 3, randomised controlled, non-inferiority trial. Lancet Respir Med. 2021 Nov;9(11):1231-1240. doi: 10.1016/S2213-2600(21)00323-4. Epub 2021 Aug 26.

  PMID: 34454654 BACKGROUND

• Kong KL, Willatts SM, Prys-Roberts C. Isoflurane compared with midazolam for sedation in the intensive care unit. BMJ. 1989 May 13;298(6683):1277-80. doi: 10.1136/bmj.298.6683.1277.

  PMID: 2500195 BACKGROUND

• 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.

  PMID: 33170331 BACKGROUND

• Jerath A, Ferguson ND, Cuthbertson B. Inhalational volatile-based sedation for COVID-19 pneumonia and ARDS. Intensive Care Med. 2020 Aug;46(8):1563-1566. doi: 10.1007/s00134-020-06154-8. Epub 2020 Jun 25.

  PMID: 32588067 BACKGROUND

• Bellgardt M, Bomberg H, Herzog-Niescery J, Dasch B, Vogelsang H, Weber TP, Steinfort C, Uhl W, Wagenpfeil S, Volk T, Meiser A. Survival after long-term isoflurane sedation as opposed to intravenous sedation in critically ill surgical patients: Retrospective analysis. Eur J Anaesthesiol. 2016 Jan;33(1):6-13. doi: 10.1097/EJA.0000000000000252.

  PMID: 25793760 BACKGROUND

• 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.

  PMID: 33528922 BACKGROUND

• Krannich A, Leithner C, Engels M, Nee J, Petzinka V, Schroder T, Jorres A, Kruse J, Storm C. Isoflurane Sedation on the ICU in Cardiac Arrest Patients Treated With Targeted Temperature Management: An Observational Propensity-Matched Study. Crit Care Med. 2017 Apr;45(4):e384-e390. doi: 10.1097/CCM.0000000000002185.

  PMID: 27941501 BACKGROUND

• Girard TD, Kress JP, Fuchs BD, Thomason JW, Schweickert WD, Pun BT, Taichman DB, Dunn JG, Pohlman AS, Kinniry PA, Jackson JC, Canonico AE, Light RW, Shintani AK, Thompson JL, Gordon SM, Hall JB, Dittus RS, Bernard GR, Ely EW. Efficacy and safety of a paired sedation and ventilator weaning protocol for mechanically ventilated patients in intensive care (Awakening and Breathing Controlled trial): a randomised controlled trial. Lancet. 2008 Jan 12;371(9607):126-34. doi: 10.1016/S0140-6736(08)60105-1.

  PMID: 18191684 BACKGROUND

• Pandharipande PP, Girard TD, Jackson JC, Morandi A, Thompson JL, Pun BT, Brummel NE, Hughes CG, Vasilevskis EE, Shintani AK, Moons KG, Geevarghese SK, Canonico A, Hopkins RO, Bernard GR, Dittus RS, Ely EW; BRAIN-ICU Study Investigators. Long-term cognitive impairment after critical illness. N Engl J Med. 2013 Oct 3;369(14):1306-16. doi: 10.1056/NEJMoa1301372.

  PMID: 24088092 BACKGROUND

• Boncyk C, Devlin JW, Faisal H, Girard TD, Hsu SH, Jabaley CS, Sverud I, Falkenhav M, Kress J, Sheppard K, Sackey PV, Hughes CG. INhaled Sedation versus Propofol in REspiratory failure in the Intensive Care Unit (INSPiRE-ICU1): protocol for a randomised, controlled trial. BMJ Open. 2024 Oct 26;14(10):e086946. doi: 10.1136/bmjopen-2024-086946.

  PMID: 39461861 DERIVED

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

• Kimberly Rengel, M.D.

  Vanderbilt University Medical Center

  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: March 11, 2022
• First Posted: April 5, 2022
• Study Start: April 28, 2022
• Primary Completion: April 26, 2024
• Study Completion: October 24, 2024
• Last Updated: March 24, 2026
• Results First Posted: March 24, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (14)