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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT03089905
Registration number
NCT03089905
Ethics application status
Date submitted
8/03/2017
Date registered
24/03/2017
Titles & IDs
Public title
A Study to Compare the Long-term Outcomes After Two Different Anaesthetics
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Scientific title
Neurodevelopmental Outcome After Standard Dose Sevoflurane Versus Low-dose Sevoflurane/Dexmedetomidine/Remifentanil Anaesthesia in Young Children- The TREX Trial
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Secondary ID [1]
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2024-512385-34-00
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Secondary ID [2]
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TREX TRIAL
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Universal Trial Number (UTN)
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Trial acronym
TREX
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Anesthesia
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Neurotoxicity
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Child Development
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Condition category
Condition code
Neurological
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Other neurological disorders
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Injuries and Accidents
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0
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Poisoning
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - Sevoflurane
Treatment: Drugs - Remifentanil
Treatment: Drugs - Dexmedetomidine
Experimental: Sevoflurane/dexmedetomidine/remifentanil - Dexmedetomidine: loading dose of 1mcg/kg over 10 minutes followed by an infusion of at 1 mcg/kg/hr.
Remifentanil: loading dose 1 mcg/kg over 2 minutes followed by an infusion starting at 0.1 mcg/kg/min or greater.
Sevoflurane: end tidal concentration of 0.6 -0.8% or less.
Active comparator: Sevoflurane - End tidal concentration of 2.5-3.0% or greater.
Treatment: Drugs: Sevoflurane
Experimental arm: end tidal concentration of 0.6 -0.8% or less. Active comparator arm: end tidal concentration of 2.5-3.0% or greater.
Treatment: Drugs: Remifentanil
Experimental arm: loading dose: 1 mcg/kg, infusion starting at 0.1 mcg/kg/min or greater.
Treatment: Drugs: Dexmedetomidine
Experimental arm: loading dose:1mcg/kg, infusion: 1 mcg/kg/hr.
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Full Scale IQ
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Assessment method [1]
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Global cognitive function as assessed by the full scale IQ score of the Wechsler Preschool and Primary School Intelligence Scale.
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Timepoint [1]
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3 years of age
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Secondary outcome [1]
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incidence of intra-operative hypotension
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Assessment method [1]
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Blood pressure measurements will be recorded during surgery
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Timepoint [1]
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150 minutes- duration of surgery (baseline)
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Secondary outcome [2]
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incidence of intra-operative bradycardia
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Assessment method [2]
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Heart rate will be recorded during surgery
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Timepoint [2]
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150 minutes- duration of surgery (baseline)
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Secondary outcome [3]
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Post-operative pain
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Assessment method [3]
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Pain scores will be recorded after surgery
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Timepoint [3]
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60 minutes- after surgery
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Secondary outcome [4]
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Time to recovery
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Assessment method [4]
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Time of removal of airway, eye-opening and discharge from PACU will be recorded.
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Timepoint [4]
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60 minutes- after surgery
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Secondary outcome [5]
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Language outcomes
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Assessment method [5]
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Clinical Evaluation of Language Fundamentals- Preschool, Version 2 (CELF-P2)
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Timepoint [5]
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3 years of age
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Secondary outcome [6]
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Attention/Executive Function/impulse control
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Assessment method [6]
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A Developmental NEuroPSYchological Assessment- Second Edition (NEPSY-2): Statue Subtest
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Timepoint [6]
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3 years of age
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Secondary outcome [7]
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Memory
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Assessment method [7]
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A Developmental NEuroPSYchological Assessment- Second Edition (NEPSY-2): Narrative memory
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Timepoint [7]
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3 years of age
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Secondary outcome [8]
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Adaptive behaviour
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Assessment method [8]
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Adaptive Behavior Assessment System - Third Edition (ABAS-III)
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Timepoint [8]
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3 years of age
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Secondary outcome [9]
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Clinical Behavior
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Assessment method [9]
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Child Behavior Checklist (CBCL)
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Timepoint [9]
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3 years of age
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Secondary outcome [10]
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Executive Function
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Assessment method [10]
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Behavior Rating of Executive Function- Preschool (BRIEF-P)
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Timepoint [10]
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3 years of age
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Secondary outcome [11]
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Social Skills
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Assessment method [11]
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Social Skills Improvement System (SSIS)
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Timepoint [11]
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3 years of age
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Eligibility
Key inclusion criteria
* Younger than 2 years (chronological age)
* Scheduled for anaesthesia that is expected to last at least 2 hours (and/or total operating room time is scheduled to be at least 2.5 hours)
* Has a legally acceptable representative capable of understanding the informed consent document and providing consent on the participant's behalf.
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Minimum age
No limit
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Maximum age
2
Years
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
* Known neurologic, chromosomal or congenital anomaly which is likely to be associated with poor neurobehavioural outcome
* Existing diagnosis of behavioural or neurodevelopmental disability
* Prematurity (defined as < 36 weeks gestational age at birth)
* Birth weight less than 2 kg.
* Congenital cardiac disease requiring surgery
* Intracranial neurosurgery and intracranial craniofacial surgery (isolated cleft lip is not an exclusion)
* Previous cumulative exposure to general anaesthesia exceeding 2 hours
* Planned future cumulative exposure to anaesthesia exceeding 2 hours before the age of 3 years.
* Any specific contra-indication to any aspect of the protocol
* Previous adverse reaction to any anaesthetic
* Circumstances likely to make long term follow-up impossible
* Living in a household where the primary language spoken at home is not a language in which we can administer the Wechsler Preschool and Primary School Intelligence Scale
* Planned postoperative sedation with any agent except opioids (e.g. benzodiazepines, dexmedetomidine, ketamine, barbiturates, propofol, clonidine, chloral hydrate, and other non-opioid sedatives). For example if such sedation is planned for post-operative ventilation
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Blinded (masking used)
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Who is / are masked / blinded?
The people assessing the outcomes
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 3
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Active, not recruiting
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
10/08/2017
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
1/06/2026
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Actual
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Sample size
Target
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Accrual to date
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Final
450
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Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
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Recruitment hospital [1]
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Sydney Children's Hospital - Randwick
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Recruitment hospital [2]
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Children's Hospital at Westmead - Westmead
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Recruitment hospital [3]
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Queensland Children's Hospital - Brisbane
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Recruitment hospital [4]
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Women's and Children's Hospital - Adelaide
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Recruitment hospital [5]
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Flinders Medical Centre - Bedford Park
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Recruitment hospital [6]
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Royal Children's Hospital - Parkville
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Recruitment hospital [7]
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Perth Children's Hospital - Perth
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Recruitment postcode(s) [1]
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2031 - Randwick
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Recruitment postcode(s) [2]
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2145 - Westmead
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Recruitment postcode(s) [3]
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4101 - Brisbane
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Recruitment postcode(s) [4]
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5006 - Adelaide
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Recruitment postcode(s) [5]
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5042 - Bedford Park
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Recruitment postcode(s) [6]
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3052 - Parkville
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Recruitment postcode(s) [7]
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6008 - Perth
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Recruitment outside Australia
Country [1]
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United States of America
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State/province [1]
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Massachusetts
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Country [2]
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United States of America
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State/province [2]
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Ohio
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Country [3]
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United States of America
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State/province [3]
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Pennsylvania
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Country [4]
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United States of America
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State/province [4]
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Texas
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Country [5]
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Italy
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State/province [5]
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Alessandria
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Country [6]
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Italy
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State/province [6]
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Bologna
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Country [7]
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Italy
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State/province [7]
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Firenze
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Country [8]
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Italy
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State/province [8]
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Genova
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Country [9]
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Italy
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State/province [9]
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Milano
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Country [10]
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Italy
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State/province [10]
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Pisa
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Country [11]
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Italy
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State/province [11]
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Roma
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Country [12]
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Spain
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State/province [12]
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Madrid
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Funding & Sponsors
Primary sponsor type
Other
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Name
Murdoch Childrens Research Institute
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Address
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Other collaborator category [1]
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Other
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Name [1]
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Sydney Children's Hospitals Network
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Address [1]
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Country [1]
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Other collaborator category [2]
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Other
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Name [2]
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Baylor College of Medicine
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Address [2]
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Other collaborator category [3]
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Other
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Name [3]
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Boston Children's Hospital
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Address [3]
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Other collaborator category [4]
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Other
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Name [4]
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The Cleveland Clinic
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Address [4]
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Other collaborator category [5]
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Other
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Name [5]
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University of Texas, Southwestern Medical Center at Dallas
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Address [5]
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Other collaborator category [6]
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Other
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Name [6]
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Royal Children's Hospital
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Address [6]
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Other collaborator category [7]
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Other
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Name [7]
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Children's Hospital of Philadelphia
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Address [7]
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Country [7]
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Other collaborator category [8]
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Other
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Name [8]
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Queensland Children's Hospital
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Address [8]
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Country [8]
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Other collaborator category [9]
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Other
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Name [9]
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Perth Children's Hospital
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Address [9]
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Other collaborator category [10]
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Other
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Name [10]
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Women and Children's Hospital
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Address [10]
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Country [10]
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Other collaborator category [11]
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Other
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Name [11]
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Istituto Giannina Gaslini
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Address [11]
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Other collaborator category [12]
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Government body
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Name [12]
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Flinders Medical Centre
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Address [12]
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Country [12]
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Ethics approval
Ethics application status
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Summary
Brief summary
There is considerable evidence that most general anaesthetics modulate brain development in animal studies. The impact is greater with longer durations of exposure and in younger animals. There is great controversy over whether or not these animal data are relevant to human clinical scenarios. The changes seen in preclinical studies are greatest with GABA agonists and NMDA antagonists such as volatile anaesthetics (eg sevoflurane), propofol, midazolam, ketamine, and nitrous oxide. There is less evidence for an effect with opioid (such as remifentanil) or with alpha 2 agonists (such as dexmedetomidine). Some, but not all, human cohort studies show an association between exposure to anaesthesia in infancy or early childhood and later changes in cognitive tests, school performance or risk of developing neurodevelopmental disorders. The evidence is weak due to possible confounding. A recent well designed cohort study (the PANDA study) comparing young children that had hernia repair to their siblings found no evidence for a difference in a range of detailed neuropsychological tests. In that study most children were exposed to up to two hours of anaesthesia. The only trial (the GAS trial) has compared children having hernia repair under regional or general anesthesia and has found no evidence for a difference in neurodevelopment when tested at two years of age. The GAS and PANDA studies confirm the animal data that short exposure is unlikely to cause any neurodevelopmental impact. The impact of longer exposures is still unknown. In humans the strongest evidence for an association between surgery and poor neurodevelopmental outcome is in infants having major surgery. However, this is also the group where confounding is most likely. The aim of our study is to see if a new combination of anaesthetic drugs results in a better long-term developmental outcome than the current standard of care for children having anaesthesia expected to last 2 hours or longer. Children will be randomised to receive either a low dose sevoflurane/remifentanil/dexmedetomidine or standard dose sevoflurane anaesthetic. They will receive a neurodevelopmental assessment at 3 years of age to assess global cognitive function.
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Trial website
https://clinicaltrials.gov/study/NCT03089905
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Andrew J Davidson, MD
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Address
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Royal Children's Hospital, Melbourne
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Country
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Phone
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Fax
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Email
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Contact person for public queries
Name
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Address
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Phone
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Fax
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Email
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Contact person for scientific queries
Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
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What data in particular will be shared?
The de-identified data set collected for this analysis of the TREX trial will be available six months after publication of the primary outcome.
The study protocol, analysis plan and consent forms will also be available. The data may be obtained from the Murdoch Children's Research Institute by emailing
[email protected]
.
Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR), Analytic code
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When will data be available (start and end dates)?
6 months after publication of primary outcome
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Available to whom?
Prior to releasing any data the following are required: a data access agreement must be signed between relevant parties, the TREX Trial Steering Committee must see and approve the analysis plan describing how the data will be analysed, there must be an agreement around appropriate acknowledgement and any additional costs involved must be covered. Data will only be shared with a recognised research institution which has approved the proposed analysis plan.
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Available for what types of analyses?
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How or where can data be obtained?
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What supporting documents are/will be available?
No Supporting Document Provided
Type
Other Details
Attachment
Statistical analysis plan
https://cdn.clinicaltrials.gov/large-docs/05/NCT03089905/SAP_000.pdf
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results not provided in
https://clinicaltrials.gov/study/NCT03089905