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

NCT ID: NCT04684238

Last Updated: 2025-05-25

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

94 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-01-14

Study Completion Date

2023-01-19

Brief Summary

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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.

Detailed Description

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This is a phase III, multi-centre, prospective, randomized, active-controlled, assessor-blind study. Primary endpoint: percentage of time of adequately maintained sedation, in absence of rescue sedation, within the COMFORT-B interval (light, moderate, or deep sedation) prescribed at randomization, monitored every 2 hours for an expected minimum of 12 hours (up to 48 hours).

Conditions

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Sedation

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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Drug: Midazolam

Midazolam for sedation in the ICU

Group Type ACTIVE_COMPARATOR

Midazolam

Intervention Type DRUG

Solution for Injection/Infusion

Drug: Isoflurane

Volatile for sedation in the ICU

Group Type EXPERIMENTAL

Isoflurane

Intervention Type DRUG

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

Interventions

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Midazolam

Solution for Injection/Infusion

Intervention Type DRUG

Isoflurane

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

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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)

Exclusion Criteria

* 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.
* Patients with acute asthma or obstructive lung disease symptoms requiring treatment at inclusion.
* 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.
Minimum Eligible Age

3 Years

Maximum Eligible Age

17 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Sedana Medical

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Peter Sackey, MD, PhD

Role: STUDY_DIRECTOR

Sedana Medical

Locations

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Hôpital Femme-Mère-Enfant Groupe Hospitalier Est

Lyon, , France

Site Status

CHU de NANTES, Hôpital Mère-Enfant

Nantes, , France

Site Status

Hôpital Robert-Debré AP-HP

Paris, , France

Site Status

Hôpitaux Universitaires Paris Sud Site Bicetre

Paris, , France

Site Status

Centre Hospitalier Universitaire de Reims

Reims, , France

Site Status

Hôpitaux Universitaires de Strasbourg Hôpital de Hautepierre

Strasbourg, , France

Site Status

Universitätsklinikum Köln

Cologne, , Germany

Site Status

Universitätsklinik Freiburg

Freiburg im Breisgau, , Germany

Site Status

Universitätsklinikum Hamburg-Eppendorf (UKE)

Hamburg, , Germany

Site Status

Universitätsklinikum Jena

Jena, , Germany

Site Status

Hospital Materno Infantil Sant Joan de Deu Hospital

Barcelona, , Spain

Site Status

Hospital Universitario Reina Sofía

Córdoba, , Spain

Site Status

Hospital General Universitario Gregorio Marañón

Madrid, , Spain

Site Status

Hospital Infantil Universitario Niño Jesús Pediatric Intensive Care Unit

Madrid, , Spain

Site Status

Hospital Universitario 12 de Octubre

Madrid, , Spain

Site Status

Hospital Universitario La Paz

Madrid, , Spain

Site Status

Hospital Regional Universitario, Carlos Haya

Málaga, , Spain

Site Status

Hospital Universitario Virgen del Rocio de Sevilla

Seville, , Spain

Site Status

Hospital Universitari i Politecnic La Fe

Valencia, , Spain

Site Status

Karolinska Universitetssjukhus Solna

Solna, , Sweden

Site Status

Leeds Teaching Hospitals NHS Trust

Leeds, , United Kingdom

Site Status

University Hospitals of Leicester NHS Trust

Leicester, , United Kingdom

Site Status

Imperial College Healthcare NHS Trust

London, , United Kingdom

Site Status

Royal Manchester Children's Hospital

Manchester, , United Kingdom

Site Status

Countries

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France Germany Spain Sweden United Kingdom

References

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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.

Reference Type BACKGROUND
PMID: 23797368 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20122588 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23643411 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22380747 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22079951 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24717461 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18614330 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16013698 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30059477 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29727363 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16699772 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15640636 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16176317 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10890677 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23778830 (View on PubMed)

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.

Reference Type DERIVED
PMID: 40680761 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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SED002

Identifier Type: -

Identifier Source: org_study_id

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