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

Study Overview
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Brief Summary
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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 1 year.

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

Conditions
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Intensive Care Units, Pediatric, Anesthetics, Inhalation

Intervention / Treatment
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* Drug: Isoflurane Inhalant Product
* Drug: Sevoflurane inhalant product


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Receiving IV sedation by infusion or bolus for ≤72h to aid mechanical ventilation (but will be recruited as early as possible). Exclusion Criteria: Current use of inhaled prostacyclin (high viscosity of prostacyclin impairs vaporizer device) Family history or personal history of malignant hyperthermia (MH) Allergy to isoflurane, sevoflurane or other volatile inhaled anesthetic gas Metabolic, mitochondrial or myopathy disease e.g., Duchenne muscular dystrophy (volatiles may trigger malignant hyperthermia like reaction) Moribund with expected survival < 24h Pregnancy or lactation Suspected or evidence of high intracranial pressure (ICP)

Ages Eligible for Study
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Minimum Age: 1 Month
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Pilot, multicenter, vanguard randomized controlled trial (RCT) to assess the feasibility of accruing patients, delivering the intervention of inhaled sedatives, and ascertaining outcomes in preparation for a definitive trial to evaluate if inhaled sedatives (intervention) compared to IV agents (comparator) improves delirium (outcome) in mechanically ventilated children (population).
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Inhaled sedation - volatile anesthetic<br>The ICU patient will receive either Isoflurane or Sevoflurane, whichever is available at the hospital. Dosage will be modified as per health care team guidance for the best treatment of the participant. | Drug: Isoflurane Inhalant Product<br>* Isoflurane will be administered using an inhalation device<br>Drug: Sevoflurane inhalant product<br>* Sevoflurane will be administered using an inhalation device<br>|
| No Intervention: IV sedation - standard of care<br>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. | |

What is the study measuring?
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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 |