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)

Sedation Clinical Trial

— INSPiRE-ICU2  

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05327296
• Other study ID #: SED004
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: June 30, 2022
• Est. completion date: December 30, 2024

Study information

• Verified date: June 2024
• Source: Sedana Medical
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 235
• Est. completion date: December 30, 2024
• Est. primary completion date: May 28, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Sedation

Intervention

Drug:
• Isoflurane
Inhaled isoflurane administered by Sedaconda ACD-S
• Propofol
Intravenous infusion of propofol

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	The Cooper Health System	Camden	New Jersey
United States	Rush University Medical Center	Chicago	Illinois
United States	Ohio State University	Columbus	Ohio
United States	University of Miami	Coral Gables	Florida
United States	Henry Ford Health System	Detroit	Michigan
United States	Memorial Hermann Health Services	Houston	Texas
United States	Memorial Health Services	Long Beach	California
United States	University of California, Los Angeles	Los Angeles	California
United States	The New York and Presbyterian Hospital	New York	New York
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Stanford University	Redwood City	California
United States	Virginia Commonwealth University	Richmond	Virginia
United States	University of California, San Diego	San Diego	California

Sponsors (1)

Lead Sponsor	Collaborator
Sedana Medical

Country where clinical trial is conducted

United States, 

References & Publications (15)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. Erratum In: JAMA. 2013 Jan 16;309(3):237. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of time adequate sedation depth	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	During study treatment up to 48 (±6) hours
Secondary	Key Secondary: Compare the use of opioids	To compare the effect of isoflurane vs propofol on use of opioids during the study drug treatment period measuring CPOT	During study treatment up to 48 (±6) hours
Secondary	Key Secondary: Compare the wake up time	To compare the effect of isoflurane vs propofol on the wake up time at end of study drug treatment	Time from stop of study drug treatment up to 4 hours
Secondary	Key Secondary: Compare the cognitive recovery after EOT	To compare the effect of isoflurane vs propofol on cognitive recovery after EOT by measuring CAM-ICU-7	60 minutes after EOT
Secondary	Key Secondary: Compare the spontaneous breathing effort	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	During study treatment up to 48 (±6) hours
Secondary	Other secondary: Compare time from sedation termination to extubation	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	During study treatment
Secondary	Other secondary: Compare days alive and free of mechanical ventilation through Study Day 30	To compare the effect of isoflurane vs propofol on days alive and free of mechanical ventilation through Study Day 30	From start of study treatment up to 30 days
Secondary	Other secondary: Compare days alive and free of the ICU	To compare the effect of isoflurane vs propofol on days alive and free of the ICU	From start of study treatment up to 30 days
Secondary	Other secondary: Compare delirium and coma free days until 7 days after EOT	To compare the effect of isoflurane vs propofol on delirium and coma free days until 7 days after EOT	From start of study treatment until 7 days after EOT
Secondary	Other secondary: Compare mortality at 30 days after randomization	To compare the effect of isoflurane vs propofol on mortality at 30 days after randomization	Until 30 days after randomization
Secondary	Other secondary: Compare mortality at 3 months after randomization	To compare the effect of isoflurane vs propofol on mortality at 3 months after randomization	Until 3 months after randomization
Secondary	Other secondary: Compare mortality at 6 months after randomization	To compare the effect of isoflurane vs propofol on mortality at 6 months after randomization	Until 6 months after randomization
Secondary	Other secondary: To compare the safety profile of isoflurane vs propofol	To compare the safety profile of isoflurane vs propofol in respect to reported Adverse Event	Baseline to end of study treatment, safety lab from baseline up to 48hrs post treatment, AEs from start study treatment up to day 30
Secondary	Other secondary: To assess Sedaconda ACD-S device deficiencies in patients receiving isoflurane	To assess Sedaconda ACD-S device deficiencies in patients receiving isoflurane by Sedaconda ACD-S by reported Adverse Event	During study treatment up to 48 (±6) hours
Secondary	Other secondary: To compare the use of restraints in patients receiving isoflurane vs propofol	Incidence of restraints measured twice daily	During study treatment up to 48 (±6) hours

External 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.