A Pooled Analysis of Long-Term Outcomes After Inhaled Isoflurane Via the Sedaconda ACD-S Compared to Intravenous Propofol

NCT06809218 | Active Not Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: SED003_SED004
• Study Type: interventional
• Target: 312
• Locations: 1 country
• Sites: 1

Brief Summary

This pooled analysis will assess Cognitive, Mental Health, Functioning, and Quality of Life Assessments data from the Phase 3 registration studies INSPiRE-ICU 1 (NCT05312385) and INSPiRE-ICU 2 (NCT05327296) to explore potential differences in Long-Term Outcomes at 3 and 6 months after treatment between critically ill mechanically ventilated patients sedated with inhaled isoflurane compared to sedated with intravenous propofol. The analyses were pre-planned and agreed prior to completion of enrollment of either study.

Conditions

Post-Intensive Care Syndrome; Sedation

Keywords

Sedation; Inhaled Sedation; Long-term Outcomes; Cognitive Outcomes; INSPiRE-ICU; Post-Traumatic Stress Disorder; Activities and Daily Living; Quality of Life

Outcome Measures

Primary Outcomes (1)

• To compare cognitive function 3 months post randomization in isoflurane- vs propofol-treated patients

  A patient is classified as cognitive impaired if the patient has a score 2 SD (or more) worse than population mean for one test or has a score 1.5 SD (or more) worse than population mean in two or more of the following tests: TICS, WAIS IV Digit Span, Hayling Sentence Completion Test, Controlled Oral Word Association, WMS IV - Immediate Memory (Adult/Older Adult) and WMS IV - Delayed Memory (Adult/Older Adult), at 3 months post randomization. The analysis will take into account age, sex, level of education, total IQCODE score at baseline, total SAPS total score at baseline, medical or surgical admission duration of mechanical ventilation before randomization, study drug and treatment duration as factors.

  3 months post Randomization

Secondary Outcomes (6)

• To compare memory panorama from time in the ICU in isoflurane- vs propofol-treated patients

  3 months post Randomization

• To compare physical outcomes and trajectories at 3 and 6 months post randomization in isoflurane- vs propofol-treated patients

  3 and 6 months post Randomization

• To compare depressive symptoms at 3 months post randomization in isoflurane- vs propofol-treated patients

  3 months post Randomization

• To compare anxiety symptoms at 3 months post randomization in isoflurane- vs propofol-treated patients

  3 months post Randomization

• To compare post-traumatic stress symptoms at 3 months post randomization in isoflurane- vs propofol-treated patients

  3 months post Randomization

Study Arms (2)

Inhaled isoflurane administered via Sedaconda ACD-S

EXPERIMENTAL

Intervention: isoflurane

Drug: Inhaled isoflurane administered by Sedaconda ACD-S

Propofol administered as intravenous infusion

ACTIVE COMPARATOR

Treatment: propofol

Drug: Intravenous infusion of propofol

Interventions

Inhaled isoflurane administered by Sedaconda ACD-S DRUG

Intervention: isoflurane

Inhaled isoflurane administered via Sedaconda ACD-S

Intravenous infusion of propofol DRUG

Intervention: propofol

Propofol administered as intravenous infusion

Eligibility Criteria

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

You may qualify if:

• \. Patients who are enrolled in INSPiRE-ICU1 (NCT05312385) or INSPiRE-ICU2 (NCT05327296) and survived to discharge.

Sponsors & Collaborators

• Sedana Medical: lead
• Critical Illness, Brain Dysfunction, and Survivorship Center: collaborator

Study Sites (1)

The Critical Illness, Brain Dysfunction and Survivorship (CIBS) Center

Nashville, Tennessee, 37203, United States

Location

Related Publications (15)

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  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.

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• 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.

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• 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.

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• 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.

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• 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.

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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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• 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.

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• 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.

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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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• 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.

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• 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.

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• 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.

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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

Conditions

postintensive care syndrome; Stress Disorders, Post-Traumatic; Motor Activity

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders; Behavior

Study Officials

• Peter Sackey, MD, PhD

  Chief Medical Officer

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: For the Long-term follow-up part of the INSPiRE-ICU 1 \& 2 studies, a separate centralized team at the Critical Illness, Brain Dysfunction and Survivorship (CIBS) center at Vanderbilt University Medical Center, is conducting the assessments and are not informed about the study treatment patients received at their respective site.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 8, 2025
• First Posted: February 5, 2025
• Study Start: April 22, 2022
• Primary Completion: November 14, 2024
• Study Completion: January 30, 2025
• Last Updated: February 5, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)