Advancing Brain Outcomes in Pediatric Critically Ill Patients Sedated With Volatile AnEsthestic Agents (ABOVE)

Advancing Brain Outcomes in Pediatric Critically Ill Patients Sedated With Volatile AnEsthestic Agents: A Pilot Multicentre Randomized Controlled Trial

The goal of a pilot study is to test a study plan to see if it is appropriate for a larger study. This study plan is looking at whether the use of inhaled sedatives (medications that help people be calm and sleep) can reduce delirium (extreme confusion) in children who need a ventilator (breathing machine) compared to IV or oral sedatives.

The main question[s] it aims to answer are:

• Will people join the study? (recruitment)
• Will participants finish the study?
• Will healthcare teams accept the study procedures?

Participants will be randomized to receive study treatment (inhaled sedation) or standard of care (IV sedation). They will be monitored daily for up to 28 days. They will complete memory, thinking and behaviour tasks after 9-12 months.

Study Overview

• Status: Recruiting
• Conditions: Anesthetics, Inhalation; Intensive Care Units, Pediatric; Mechanically Ventilated, Critically Ill Children
• Intervention / Treatment: Drug: Isoflurane Inhalant Product

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Sunnybrook Research Institute, Program Manager - Centre for Clinical Trials Services; Phone Number: 416-480-6100; Email: ABOVETrial@sunnybrook.ca

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8N 3Z5
      • Recruiting
      • McMaster Children's Hospital
      • Contact: Sherrie Orr; Phone Number: 75824 905-521-2100; Email: orrs@mcmaster.ca
      • Contact: Marina Mir-Parramon; Email: mirparrm@mcmaster.ca
      • Principal Investigator: Marina Mir-Parramon, MD
    • London, Ontario, Canada, N6A 5W9
      • Recruiting
      • Children's Hospital - London Health Sciences Centre
      • Principal Investigator: Rishi Ganesan, MD, DM
      • Contact: Maysaa Assaf; Phone Number: 77548 519-685-8500; Email: Maysaa.Assaf@lhsc.on.ca
      • Contact: Rishi Ganesan; Email: Rishi.Ganesan@lhsc.on.ca
    • Toronto, Ontario, Canada, M5G 1X8
      • Recruiting
      • The Hospital for Sick Children (SickKids)
      • Principal Investigator: Nicole McKinnon, MD, PhD
      • Contact: Nicole McKinnon; Email: nicole.mckinnon@sickkids.ca
      • Contact: Stephanie DeLorenzo; Phone Number: 414712 416-813-7654; Email: stephanie.delorenzo@sickkids.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Pediatric patients age from 1 month to less than 18 years who need sedation to tolerate mechanical ventilation and will remain ventilated for ≥ 24 hours
2. Receiving IV sedation by infusion or bolus for ≤72h to aid mechanical ventilation (but will be recruited as early as possible)

Exclusion Criteria:

1. Current use of inhaled prostacyclin (high viscosity of prostacyclin impairs vaporizer device) or continuous salbutamol nebulization (impairs gas analyzer function)
2. Family history or personal history of malignant hyperthermia (MH)
3. Allergy to isoflurane, sevoflurane or other volatile inhaled anesthetic gas
4. Metabolic, mitochondrial or myopathy disease e.g., Duchenne muscular dystrophy (volatiles may trigger malignant hyperthermia like reaction)
5. Moribund with expected survival < 24h
6. Known pregnancy or lactation
7. Suspected or evidence of high intracranial pressure (ICP)
8. Not a 'closed ventilator circuit' with potential for gas leak (e.g. uncuffed ETT, bronchopleural fistula, tracheal/trachea-esophageal fistulas, or other sources of "gas leak" from patient circuit that cannot be removed)
9. Prior enrollment in the ABOVE trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: IV sedation - standard of care; The ICU patient will receive standard of care, which is IV sedation supplied by the hospital. Dosage will be modified as per health care team guidance for the best treatment of the participant.
Experimental: Inhaled sedation - volatile anesthetic; The ICU patient will receive Isoflurane. Dosage will be modified as per health care team guidance for the best treatment of the participant.	Drug: Isoflurane Inhalant Product; Isoflurane will be administered using an inhalation device

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Participant recruitment	Accrual and/or identification of challenges in accruing 60 mechanically ventilated participants (age 1 month to 18 years).	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Protocol adherence	The frequency (%) of randomized patients who remain within their designated trial arm and cross-overs. Cross overs may occur from i) drug allergy (rare <0.1%), ii) clinical reason, iii) equipment issues, and iv) health team discomfort using a new intervention.	28 days
Attrition	The frequency (%) of randomized patients who are lost to follow up prior to completion of all study outcome measures and the reasons for no follow-up will be documented. Expected loss to follow-up can occur due to i) inter-facility transfers, ii) patient/family withdrawal from the trial, iii) lack of interest in long-term follow-up.	3 years
Safety/adverse event rate	Adverse events that are assess as related (possibly, probably or definitely) to study intervention, standard of care, or study equipment will be reported. Adverse events that are assess as unrelated to study intervention, standard of care or study equipment will not be reported. Adverse events will be captured from the time of consent until the time of study completion.	From date of consent until the date of resolution or date of death from any cause, whichever came first, assessed up to 13 months
Healthcare team satisfaction	All health team members (physicians, nurses and respiratory therapists) will be surveyed daily for up to 3 days in both study arms using a 5-point Likert scale satisfaction score. Free text comments will be allowed to better understand barriers and facilitators.	Study days 1, 2 & 3

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of collecting delirium scores	Proportion of participants who complete delirium (Cornell Assessment of Pediatric Delirium (CAPD)) and coma (Richmond Agitation Sedation Scale (RASS) or COMFORT Behavioural Scale (COMFORT-B)) assessments twice a day.	28 days
Delirium-free Coma-free days	The number of full days participants do not experience coma or delirium as assessed by RASS or COMFORT-B for coma and CAPD for delirium.	28 days
Anti-psychotic drug use	The administration of anti-psychotic drugs will be captured from baseline until day 28.	28 days
Sedative drug use	The administration of sedative drugs will be captured from baseline until day 28.	28 days
Blood collection to assess biological markers of delirium, inflammation and brain injury	Participants over >2 years old will be able to participate in an optional blood collection sub-study that will look at 60 markers of delirium, inflammation and brain injury.	Study days 1, 2 & 3
Feasibility of neurocognitive assessment	Proportion of participants who complete 12 month neurocognitive assessment	1-year post enrollment
Neurocognitive scores	Assessment of scores from age-appropriate neurocognitive tests completed at 12-months post enrollment	1-year post enrollment
In-hospital mortality	Participant survival status will be captured daily for 28 days and reported at hospital discharge	1 year
Ventilator-free days	The use of a ventilator will be captured from baseline until day 28. The number of days a participant does not require a ventilator will be computed.	28 days
ICU-free days	ICU discharge date will be captured and compared to admission date to determine number of days the participant was not in the ICU up to 28 days.	28 days

Collaborators and Investigators

• Sponsor: Sunnybrook Health Sciences Centre
• Collaborators: Canadian Institutes of Health Research (CIHR)
• Investigators: Principal Investigator: Angela Jerath, MD, Sunnybrook Health Sciences Centre

Study record dates

Study Major Dates

• Study Start (Actual): October 10, 2023
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: May 2, 2023
• First Submitted That Met QC Criteria: May 10, 2023
• First Posted (Actual): May 22, 2023

Study Record Updates

• Last Update Posted (Actual): February 4, 2026
• Last Update Submitted That Met QC Criteria: February 2, 2026
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Pathological Conditions, Signs and Symptoms; Respiratory Aspiration; Physiological Effects of Drugs; Anesthetics; Central Nervous System Depressants; Platelet Aggregation Inhibitors; Anesthetics, General; Anesthetics, Inhalation; Sevoflurane; Isoflurane
• Other Study ID Numbers: CTO - 4285

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No