Skip to main content
OpenTrials
Completed

NCT Number: NCT04684238

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

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Sedation

Age range

3 year–17 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Hôpital Femme-Mère-Enfant Groupe Hospitalier Est, Lyon, France

Loading trial locations.

About this study

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).

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

midazolam

Drug

Solution for Injection/Infusion

Isoflurane

Drug

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

Primary outcomes

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

    Time frame: Minimum of 12 hours 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)

Secondary outcomes

  1. Compare the Use of Opioids

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

    Dose of opioids from first blinded COMFORT-B assessment (at +2 h from start of study drug) to end of study treatment period. This was a key secondary efficacy endpoint. Dose of opioids was expressed as fentanyl IV equivalents.

  2. Compare the Use of Opioids

    Time frame: 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).

    Dose of opioids during the last 4 h of study treatment, as compared to the first 4 h of study treatment after first blinded COMFORT-B assessment. This was a key secondary efficacy endpoint. Dose of opioids is expressed as fentanyl IV equivalents.

  3. Compare Time From End of Study Drug Administration to Extubation

    Time frame: From end of study drug administration to extubation or end of extubation attempt

    Time from end of study drug administration to extubation if study drug was terminated for extubation

  4. Compare the Proportion of Time With Spontaneous Breathing

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

    Proportion of observations with spontaneous breathing efforts during study treatment. This was a key secondary safety endpoint.

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

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

    Need for additional inotropic/vasopressor agent defined by change in Vasoactive-Inotropic Score (VIS) during study treatment period compared to baseline.

    The VIS quantifies the amount of cardiovascular support required by infants postoperatively according to the below calculation:

    VIS = dopamine (µg/kg/min) + dobutamine (µg/kg/min) + 100 × epinephrine (µg/kg/min) + 100 × norepinephrine (µg/kg/min) + 10 × milrinone (µg/kg/min) + 10,000 × vasopressin (U/kg/min).

    An increased VIS score correlates to an increase in inotropic/vasopressor agents.

  6. Evaluate the Number of Patients With Withdrawal Symptom

    Time frame: From > 96 hours sedation (including pre-study sedation period) until the end of the 48-hour post study treatment monitoring or ICU discharge, whichever comes first.

    Evaluate the frequency of withdrawal symptoms in isoflurane- vs midazolam-treated patients according to SOS-PD.

  7. Evaluate the Frequency of Delirium

    Time frame: Patients admitted to the ICU ≥48 hours (including period prior to study enrolment) until the end of the 48-hour post study treatment monitoring or ICU discharge, whichever comes first.

    Evaluate the frequency of delirium in isoflurane- vs midazolam-treated patients

  8. Evaluate the Frequency of Neurological Symptoms or Psychomotor Dysfunction

    Time frame: During study treatment and up to 48 hours after discontinuation of isoflurane and midazolam

    Evaluate the frequency of neurological symptoms or psychomotor dysfunction during and up to 48 hours after discontinuation of isoflurane and midazolam treatment, and the association with duration of treatment, and total exposure (MAC hours and midazolam doses) over time.

  9. Compare the 30 Days/Hospital Mortality

    Time frame: From start of study treatment up to 30 days

    Compare the 30 days/hospital mortality in isoflurane- vs midazolam-treated patients

  10. Compare Ventilator-free Days

    Time frame: From start of study treatment up to 30 days

    Ventilator-free days at 30 days from start of study treatment period.

  11. Compare the Time in ICU/Hospital

    Time frame: From start of study treatment up to 30 days

    Compare the time in ICU at 30 days from start of study treatment period. This was a secondary safety endpoint. Patients that were withdrawn prior to day 30 were excluded from the analysis. Patients who died before day 30 were not considered withdrawals. For these patients, the days in ICU until day of death were considered ICU days.

  12. Compare ICU-free Days

    Time frame: From start of study treatment up to 30 days

    Compare ICU-free days up to 30 days in isoflurane- vs midazolam-treated patients.

Sponsors and collaborators

Lead sponsor

Sedana Medical

Industry

Registry information

Official study title

A Randomised Active-controlled Study to Compare Efficacy & Safety of Inhaled Isoflurane Delivered by the AnaConDa-S (Anaesthetic Conserving Device) vs IV Midazolam for Sedation in Mechanically Ventilated Paediatric Patients 3-17 Years Old

Acronym: IsoCOMFORT

Important dates

Study start
2021
Primary completion
2023
Study completion
2023
First posted
Dec 24, 2020
Registry last updated
May 25, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.