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

Intensive Care Units, Pediatric Clinical Trial

— ABOVE  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05867472
• Other study ID #: CTO - 4285
• Status: Recruiting
• Phase: Phase 3
• Start date: October 10, 2023
• Est. completion date: May 2026

Study information

• Verified date: October 2023
• Source: Sunnybrook Health Sciences Centre
• Contact: Sunnybrook Research Institute, Program Manager - Centre for Clin
• Phone: 416-480-6100
• Email: ABOVETrial[@]sunnybrook.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: May 2026
• Est. primary completion date: May 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Month to 18 Years

Eligibility

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)

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. Pregnancy or lactation

7. Suspected or evidence of high intracranial pressure (ICP)

Related Conditions & MeSH terms

• Anesthetics, Inhalation
• Critical Illness
• Intensive Care Units, Pediatric
• Respiratory Aspiration

Intervention

Drug:
• Isoflurane Inhalant Product
Isoflurane will be administered using an inhalation device
• Sevoflurane inhalant product
Sevoflurane will be administered using an inhalation device

Locations

Country	Name	City	State
Canada	Children's Hospital - London Health Sciences Centre	London	Ontario
Canada	The Hospital for Sick Children (SickKids)	Toronto	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
Sunnybrook Health Sciences Centre	Canadian Institutes of Health Research (CIHR)

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	Anti-psychotic drug use	The administration of anti-psychotic drugs will be captured from baseline until day 28.	28 days
Other	Sedative drug use	The administration of sedative drugs will be captured from baseline until day 28.	28 days
Other	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
Other	Feasibility of neurocognitive assessment	Proportion of participants who complete 12 month neurocognitive assessment	1-year post enrollment
Other	Neurocognitive scores	Assessment of scores from age-appropriate neurocognitive tests completed at 12-months post enrollment	1-year post enrollment
Other	In-hospital mortality	Participant survival status will be captured daily for 28 days and reported at hospital discharge	1 year
Other	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
Other	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
Primary	Participant recruitment	Accrual and/or identification of challenges in accruing 60 mechanically ventilated participants (age 1 month to 18 years).	2 years
Secondary	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
Secondary	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
Secondary	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
Secondary	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