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

Primary Purpose

Intensive Care Units, Pediatric, Anesthetics, Inhalation

Status
Not yet recruiting
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Isoflurane Inhalant Product
Sevoflurane inhalant product
Sponsored by
Sunnybrook Health Sciences Centre
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Intensive Care Units, Pediatric

Eligibility Criteria

1 Month - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    No Intervention

    Arm Label

    Inhaled sedation - volatile anesthetic

    IV sedation - standard of care

    Arm Description

    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.

    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.

    Outcomes

    Primary Outcome Measures

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

    Secondary Outcome Measures

    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.
    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.
    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.
    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.

    Full Information

    First Posted
    May 2, 2023
    Last Updated
    May 10, 2023
    Sponsor
    Sunnybrook Health Sciences Centre
    Collaborators
    Canadian Institutes of Health Research (CIHR)
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05867472
    Brief Title
    Advancing Brain Outcomes in Pediatric Critically Ill Patients Sedated With Volatile AnEsthestic Agents
    Acronym
    ABOVE
    Official Title
    Advancing Brain Outcomes in Pediatric Critically Ill Patients Sedated With Volatile AnEsthestic Agents: A Pilot Multicentre Randomized Controlled Trial
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    May 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    June 2023 (Anticipated)
    Primary Completion Date
    May 2026 (Anticipated)
    Study Completion Date
    May 2026 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Sunnybrook Health Sciences Centre
    Collaborators
    Canadian Institutes of Health Research (CIHR)

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief 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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Intensive Care Units, Pediatric, Anesthetics, Inhalation

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    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
    Outcomes Assessor
    Masking Description
    This is an open label trial that will be blinded to the outcome assessor and data analyst, but not to the clinical team. Blinding is not feasible for the clinical team and patient / family given the easily identifiable differences in the nature of the essential equipment used between the two arms.
    Allocation
    Randomized
    Enrollment
    60 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Inhaled sedation - volatile anesthetic
    Arm Type
    Experimental
    Arm Description
    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.
    Arm Title
    IV sedation - standard of care
    Arm Type
    No Intervention
    Arm Description
    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.
    Intervention Type
    Drug
    Intervention Name(s)
    Isoflurane Inhalant Product
    Intervention Description
    Isoflurane will be administered using an inhalation device
    Intervention Type
    Drug
    Intervention Name(s)
    Sevoflurane inhalant product
    Intervention Description
    Sevoflurane will be administered using an inhalation device
    Primary Outcome Measure Information:
    Title
    Participant recruitment
    Description
    Accrual and/or identification of challenges in accruing 60 mechanically ventilated participants (age 1 month to 18 years).
    Time Frame
    2 years
    Secondary Outcome Measure Information:
    Title
    Protocol adherence
    Description
    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.
    Time Frame
    28 days
    Title
    Attrition
    Description
    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.
    Time Frame
    3 years
    Title
    Safety/adverse event rate
    Description
    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.
    Time Frame
    From date of consent until the date of resolution or date of death from any cause, whichever came first, assessed up to 13 months
    Title
    Healthcare team satisfaction
    Description
    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.
    Time Frame
    Study days 1, 2 & 3
    Other Pre-specified Outcome Measures:
    Title
    Feasibility of collecting delirium scores
    Description
    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.
    Time Frame
    28 days
    Title
    Delirium-free Coma-free days
    Description
    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.
    Time Frame
    28 days
    Title
    Anti-psychotic drug use
    Description
    The administration of anti-psychotic drugs will be captured from baseline until day 28.
    Time Frame
    28 days
    Title
    Sedative drug use
    Description
    The administration of sedative drugs will be captured from baseline until day 28.
    Time Frame
    28 days
    Title
    Blood collection to assess biological markers of delirium, inflammation and brain injury
    Description
    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.
    Time Frame
    Study days 1, 2 & 3
    Title
    Feasibility of neurocognitive assessment
    Description
    Proportion of participants who complete 12 month neurocognitive assessment
    Time Frame
    1-year post enrollment
    Title
    Neurocognitive scores
    Description
    Assessment of scores from age-appropriate neurocognitive tests completed at 12-months post enrollment
    Time Frame
    1-year post enrollment
    Title
    In-hospital mortality
    Description
    Participant survival status will be captured daily for 28 days and reported at hospital discharge
    Time Frame
    1 year
    Title
    Ventilator-free days
    Description
    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.
    Time Frame
    28 days
    Title
    ICU-free days
    Description
    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.
    Time Frame
    28 days

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    1 Month
    Maximum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    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)
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Sunnybrook Research Institute, Program Manager - Centre for Clinical Trials Services
    Phone
    416-480-6100
    Email
    ABOVETrial@sunnybrook.ca
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Angela Jerath, MD
    Organizational Affiliation
    Sunnybrook Health Sciences Centre
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Learn more about this trial

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

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