Effect & Safety of Inhaled Isoflurane vs IV Midazolam for Sedation in Mechanically Ventilated Children 3-17 Years Old

NCT04684238 | Completed Phase 3 Results DMC

• 1 other identifier: SED002
• Study Type: interventional
• Target: 94
• Locations: 5 countries
• Sites: 24

Brief Summary

This is a study to compare safety and efficacy of inhaled isoflurane delivered by the AnaConDa-S (Anaesthetic Conserving Device (ACD)) versus intravenous midazolam for sedation in mechanically ventilated children admitted to an intensive care unit.

Conditions

Sedation

Keywords

sedation; isoflurane; mechanically ventilation; pediatric; midazolam

Outcome Measures

Primary Outcomes (1)

• Percentage of Time of Adequately Maintained Sedation Depth up to 48 Hours (± 6 Hours)

  Percentage of time of adequately maintained sedation within the COMFORT-B interval (light, moderate or deep sedation) prescribed at randomisation, monitored every 2 h for a minimum of 12 h (up to 48 h ± 6 h)

  Minimum of 12 hours up to 48 hours (± 6 hours).

Secondary Outcomes (12)

• Compare the Use of Opioids

  From first blinded COMFORT-B assessment (at +2 h from start of study drug initiation) to end of the study treatment period

• Compare the Use of Opioids

  Last 4 hours of study treatment compared to first 4 hours of study treatment after first blinded COMFORT-B assessment (at +2 h from start of study drug initiation).

• Compare Time From End of Study Drug Administration to Extubation

  From end of study drug administration to extubation or end of extubation attempt

• Compare the Proportion of Time With Spontaneous Breathing

  From initiation of study drug treatment to End of study treatment (up to 48h +/- 6h)

• Evaluate Haemodynamic Effect as Indicated by Need for Additional Inotropic/Vasopressor Agent

  From start of study treatment to end of study treatment (up to 48h +/- 6h)

Study Arms (2)

Drug: Midazolam

ACTIVE COMPARATOR

Midazolam for sedation in the ICU

Drug: Midazolam

Drug: Isoflurane

EXPERIMENTAL

Volatile for sedation in the ICU

Drug: Isoflurane

Interventions

Midazolam DRUG

Solution for Injection/Infusion

Drug: Midazolam

Isoflurane DRUG

Inhalation vapour, liquid. Isoflurane delivered by the AnaConDa-S (Anaesthetic Conserving Device)

Drug: Isoflurane

Eligibility Criteria

• Age: 3 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Patients at least 3 years to 17 (less than 18) years at the time of randomization, admitted to an ICU/with planned ICU admission.
• Expected mechanical (invasive) ventilation and sedation for at least 12 hours.
• Informed consent obtained from the patient, patient's legal guardian(s)

You may not qualify if:

• Ongoing seizures requiring acute treatment.
• Continuous sedation for more than 72 hours at time of randomization.
• Less than 24 hours post cardiopulmonary resuscitation.
• Uncompensated circulatory shock.
• Known or suspected genetic susceptibility to malignant hyperthermia.
• Patient with tidal volume below 30 mL or above 800 mL.
• Inability to perform reliable COMFORT-B assessment in the opinion of the Investigator
• Patients with intracranial pressure (ICP) monitoring or with suspected increase in ICP
• Patients with treatment-induced whole-body hypothermia.
• Patients with pheochromocytoma.
• Patients with prolonged QT interval or with significant risk for prolonged QT interval.
• Patient not expected to survive next 48 hours or not committed to full medical care.

Sponsors & Collaborators

• Sedana Medical: lead

Study Sites (24)

Hôpital Femme-Mère-Enfant Groupe Hospitalier Est

Lyon, France

Location

CHU de NANTES, Hôpital Mère-Enfant

Nantes, France

Location

Hôpital Robert-Debré AP-HP

Paris, France

Location

Hôpitaux Universitaires Paris Sud Site Bicetre

Paris, France

Location

Centre Hospitalier Universitaire de Reims

Reims, France

Location

Hôpitaux Universitaires de Strasbourg Hôpital de Hautepierre

Strasbourg, France

Location

Universitätsklinikum Köln

Cologne, Germany

Location

Universitätsklinik Freiburg

Freiburg im Breisgau, Germany

Location

Universitätsklinikum Hamburg-Eppendorf (UKE)

Hamburg, Germany

Location

Universitätsklinikum Jena

Jena, Germany

Location

Hospital Materno Infantil Sant Joan de Deu Hospital

Barcelona, Spain

Location

Hospital Universitario Reina Sofía

Córdoba, Spain

Location

Hospital General Universitario Gregorio Marañón

Madrid, Spain

Location

Hospital Infantil Universitario Niño Jesús Pediatric Intensive Care Unit

Madrid, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, Spain

Location

Hospital Universitario La Paz

Madrid, Spain

Location

Hospital Regional Universitario, Carlos Haya

Málaga, Spain

Location

Hospital Universitario Virgen del Rocio de Sevilla

Seville, Spain

Location

Hospital Universitari i Politecnic La Fe

Valencia, Spain

Location

Karolinska Universitetssjukhus Solna

Solna, Sweden

Location

Leeds Teaching Hospitals NHS Trust

Leeds, United Kingdom

Location

University Hospitals of Leicester NHS Trust

Leicester, United Kingdom

Location

Imperial College Healthcare NHS Trust

London, United Kingdom

Location

Royal Manchester Children's Hospital

Manchester, United Kingdom

Location

Related Publications (16)

• Eifinger F, Hunseler C, Roth B, Vierzig A, Oberthuer A, Mehler K, Kribs A, Menzel C, Trieschmann U. Observations on the effects of inhaled isoflurane in long-term sedation of critically Ill children using a modified AnaConDa(c)-system. Klin Padiatr. 2013 Jul;225(4):206-11. doi: 10.1055/s-0033-1345173. Epub 2013 Jun 24.

  PMID: 23797368 BACKGROUND

• Ariyama J, Hayashida M, Shibata K, Sugimoto Y, Imanishi H, O-oi Y, Kitamura A. Risk factors for the development of reversible psychomotor dysfunction following prolonged isoflurane inhalation in the general intensive care unit. J Clin Anesth. 2009 Dec;21(8):567-73. doi: 10.1016/j.jclinane.2009.01.011.

  PMID: 20122588 BACKGROUND

• Grant MJ, Balas MC, Curley MA; RESTORE Investigative Team. Defining sedation-related adverse events in the pediatric intensive care unit. Heart Lung. 2013 May-Jun;42(3):171-6. doi: 10.1016/j.hrtlng.2013.02.004.

  PMID: 23643411 BACKGROUND

• Hoemberg M, Vierzig A, Roth B, Eifinger F. Plasma fluoride concentrations during prolonged administration of isoflurane to a pediatric patient requiring renal replacement therapy. Paediatr Anaesth. 2012 Apr;22(4):412-3. doi: 10.1111/j.1460-9592.2012.03814.x. No abstract available.

  PMID: 22380747 BACKGROUND

• Kruessell MA, Udink ten Cate FE, Kraus AJ, Roth B, Trieschmann U. Use of propofol in pediatric intensive care units: a national survey in Germany. Pediatr Crit Care Med. 2012 May;13(3):e150-4. doi: 10.1097/PCC.0b013e3182388a95.

  PMID: 22079951 BACKGROUND

• Kudchadkar SR, Yaster M, Punjabi NM. Sedation, sleep promotion, and delirium screening practices in the care of mechanically ventilated children: a wake-up call for the pediatric critical care community*. Crit Care Med. 2014 Jul;42(7):1592-600. doi: 10.1097/CCM.0000000000000326.

  PMID: 24717461 BACKGROUND

• Nolent P, Laudenbach V. [Sedation and analgesia in the paediatric intensive care unit]. Ann Fr Anesth Reanim. 2008 Jul-Aug;27(7-8):623-32. doi: 10.1016/j.annfar.2008.04.014. Epub 2008 Jul 9. French.

  PMID: 18614330 BACKGROUND

• Meiser A, Laubenthal H. Inhalational anaesthetics in the ICU: theory and practice of inhalational sedation in the ICU, economics, risk-benefit. Best Pract Res Clin Anaesthesiol. 2005 Sep;19(3):523-38. doi: 10.1016/j.bpa.2005.02.006.

  PMID: 16013698 BACKGROUND

• Meyburg J, Dill ML, von Haken R, Picardi S, Westhoff JH, Silver G, Traube C. Risk Factors for the Development of Postoperative Delirium in Pediatric Intensive Care Patients. Pediatr Crit Care Med. 2018 Oct;19(10):e514-e521. doi: 10.1097/PCC.0000000000001681.

  PMID: 30059477 BACKGROUND

• Mody K, Kaur S, Mauer EA, Gerber LM, Greenwald BM, Silver G, Traube C. Benzodiazepines and Development of Delirium in Critically Ill Children: Estimating the Causal Effect. Crit Care Med. 2018 Sep;46(9):1486-1491. doi: 10.1097/CCM.0000000000003194.

  PMID: 29727363 BACKGROUND

• Playfor S, Jenkins I, Boyles C, Choonara I, Davies G, Haywood T, Hinson G, Mayer A, Morton N, Ralph T, Wolf A; United Kingdom Paediatric Intensive Care Society Sedation; Analgesia and Neuromuscular Blockade Working Group. Consensus guidelines on sedation and analgesia in critically ill children. Intensive Care Med. 2006 Aug;32(8):1125-36. doi: 10.1007/s00134-006-0190-x. Epub 2006 May 13.

  PMID: 16699772 BACKGROUND

• Sackey PV, Martling CR, Granath F, Radell PJ. Prolonged isoflurane sedation of intensive care unit patients with the Anesthetic Conserving Device. Crit Care Med. 2004 Nov;32(11):2241-6. doi: 10.1097/01.ccm.0000145951.76082.77.

  PMID: 15640636 BACKGROUND

• Sackey PV, Martling CR, Radell PJ. Three cases of PICU sedation with isoflurane delivered by the 'AnaConDa'. Paediatr Anaesth. 2005 Oct;15(10):879-85. doi: 10.1111/j.1460-9592.2005.01704.x.

  PMID: 16176317 BACKGROUND

• Tobias JD. Tolerance, withdrawal, and physical dependency after long-term sedation and analgesia of children in the pediatric intensive care unit. Crit Care Med. 2000 Jun;28(6):2122-32. doi: 10.1097/00003246-200006000-00079.

  PMID: 10890677 BACKGROUND

• Vet NJ, Ista E, de Wildt SN, van Dijk M, Tibboel D, de Hoog M. Optimal sedation in pediatric intensive care patients: a systematic review. Intensive Care Med. 2013 Sep;39(9):1524-34. doi: 10.1007/s00134-013-2971-3. Epub 2013 Jun 19.

  PMID: 23778830 BACKGROUND

• Miatello J, Palacios-Cuesta A, Radell P, Oberthuer A, Playfor S, Amores-Hernandez I, Barreault S, Biedermann R, Charlo Molina MT, Encarnacion Martinez J, Kuehne B, Mencia S, Mendez MD, Menzel C, Morin L, Oviedo L, Piloquet JE, Falkenhav M, Sackey P, Trieschmann U, Tissieres P; IsoCOMFORT Study Group. Inhaled isoflurane for sedation of mechanically ventilated children in intensive care (IsoCOMFORT): a multicentre, randomised, active-control, assessor-masked, non-inferiority phase 3 trial. Lancet Respir Med. 2025 Oct;13(10):897-910. doi: 10.1016/S2213-2600(25)00203-6. Epub 2025 Jul 15.

  PMID: 40680761 DERIVED

MeSH Terms

Interventions

Midazolam; Isoflurane

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Methyl Ethers; Ethers; Organic Chemicals

Results Point of Contact

• Title: Ida Sverud
• Organization: Sedana Medical AB

medinfo@sedanamedical.com

+46 8 124 052 00

Study Officials

• Peter Sackey, MD, PhD

  Sedana Medical

  STUDY DIRECTOR

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: December 18, 2020
• First Posted: December 24, 2020
• Study Start: January 14, 2021
• Primary Completion: January 19, 2023
• Study Completion: January 19, 2023
• Last Updated: May 25, 2025
• Results First Posted: May 25, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1); GB (4); FR (6); DE (4); ES (9)