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A Multi-site Randomized Controlled Trial Comparing Regional and General Anesthesia for Effects on Neurodevelopmental Outcome and Apnea in Infants (GAS)

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ClinicalTrials.gov Identifier: NCT00756600
Recruitment Status : Completed
First Posted : September 22, 2008
Results First Posted : April 29, 2020
Last Update Posted : April 29, 2020
Sponsor:
Collaborators:
Royal Children's Hospital
Royal Hospital for Sick Children
Murdoch Childrens Research Institute
Food and Drug Administration (FDA)
Information provided by (Responsible Party):
Mary Ellen McCann, Boston Children's Hospital

Tracking Information
First Submitted Date  ICMJE September 18, 2008
First Posted Date  ICMJE September 22, 2008
Results First Submitted Date  ICMJE March 19, 2020
Results First Posted Date  ICMJE April 29, 2020
Last Update Posted Date April 29, 2020
Actual Study Start Date  ICMJE October 23, 2006
Actual Primary Completion Date June 30, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 16, 2020)
Full Scale IQ Score [ Time Frame: At 5 years chronological age ]
The primary outcome will be the Wechsler Preschool and Primary Scale of Intelligence-Third Edition (WPPSI-III) full scale IQ score. Verbal, visuo-spatial and processing speed skills are incorporated into the Full Scale IQ score, which is indicative of general intellectual ability. Minimum score: 45 Maximum score:145 Higher scores are associated with higher IQ scores (better outcome). Note: Scale ranges represent estimates that are very likely to be accurate but which will be verified after access to the physical assessment booklets is restored. The current health situation prohibits the research team from verifying this information at the moment.
Original Primary Outcome Measures  ICMJE
 (submitted: September 19, 2008)
The primary outcome will be the Wechsler Preschool and Primary Scale of Intelligence-Third Edition (WPPSI-III)full scale IQ score. [ Time Frame: At 5 years corrected age ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 16, 2020)
  • Verbal IQ [ Time Frame: At 5 years corrected age. ]
    Wechsler Preschool and Primary Scale of Intelligence, Third Edition (WPPSI-III): Verbal IQ Minimum possible score:45 Maximum possible score:145 A higher score indicates higher verbal IQ (better outcome). Note: Scale ranges represent estimates that are very likely to be accurate but which will be verified after access to the physical assessment booklets is restored. The current health situation prohibits the research team from verifying this information at the moment.
  • Performance IQ [ Time Frame: At 5 years corrected age ]
    Wechsler Preschool and Primary Scale of Intelligence, Third Edition (WPPSI-III): Performance IQ Minimum possible score:45 Maximum possible score:145 A higher score indicates a higher performance IQ (better outcome). Note: Scale ranges represent estimates that are very likely to be accurate but which will be verified after access to the physical assessment booklets is restored. The current health situation prohibits the research team from verifying this information at the moment.
  • Processing Speed Quotient [ Time Frame: At 5 years corrected age ]
    Wechsler Preschool and Primary Scale of Intelligence, Third Edition (WPPSI-III): Processing speed quotient Minimum possible score:45 Maximum possible score:145 A higher score indicates a better outcome. Note: Scale ranges represent estimates that are very likely to be accurate but which will be verified after access to the physical assessment booklets is restored. The current health situation prohibits the research team from verifying this information at the moment.
  • Sentence Repetition Scaled Score [ Time Frame: At 5 years chronological age ]
    Developmental Neuropsychological Assessment second edition (NEPSY-II) sub test: Sentence Repetition scaled score Minimum possible score: 1 Maximum possible score: 19 A higher score indicates a better outcome.
  • Auditory Attention Combined Scaled Score [ Time Frame: At 5 years corrected age ]
    Developmental Neuropsychological Assessment Second Edition (NEPSY-II) Sub Test: Auditory Attention combined scaled score Minimum possible score: 1 Maximum possible score: 19 A higher score indicates a better outcome.
  • Statue Scaled Score [ Time Frame: At 5 years corrected age ]
    Developmental Neuropsychological Assessment Second Edition (NEPSY-II) Sub Test: Statue scaled score Minimum possible score: 1 Maximum possible score: 19 A higher score indicates a better outcome.
  • Inhibition Combined Scaled Score [ Time Frame: At 5 years corrected age ]
    Developmental Neuropsychological Assessment Second Edition (NEPSY-II) Sub Test: Inhibition combined scaled score Minimum possible score: 1 Maximum possible score: 19 A higher score indicates a better outcome.
  • Word Generation Scaled Score [ Time Frame: At 5 years corrected age ]
    Developmental Neuropsychological Assessment Second Edition (NEPSY-II) Sub Test: Word Generation Scaled score Minimum possible score: 1 Maximum possible score: 19 A higher score indicates a better outcome.
  • Affect Recognition Scaled Score [ Time Frame: At 5 years corrected age ]
    Developmental Neuropsychological Assessment Second Edition (NEPSY-II) Sub Test: Affect Recognition scaled score Minimum possible score: 1 Maximum possible score: 19 A higher score indicates a better outcome.
  • Memory for Names and Memory for Names Delay [ Time Frame: At 5 years corrected age ]
    Developmental Neuropsychological Assessment Second Edition (NEPSY-II) Sub Test: Memory for Names and Memory for Names Delay Minimum possible score: 1 Maximum possible score: 19 A higher score indicates a better outcome.
  • Theory of Mind Scaled Score [ Time Frame: At 5 years corrected age ]
    Developmental Neuropsychological Assessment Second Edition (NEPSY-II) Sub Test: Theory of Mind scaled score Minimum possible score: 1 Maximum possible score: 19 A higher score indicates a better outcome.
  • Speeded Naming Combined Scaled Score [ Time Frame: At 5 years corrected age ]
    Developmental Neuropsychological Assessment Second Edition (NEPSY-II) Sub Test: Speeded Naming combined scaled score Minimum possible score: 1 Maximum possible score: 19 A higher score indicates a better outcome.
  • Fingertip Tapping Repetitions Scaled Score [ Time Frame: At 5 years corrected age ]
    Developmental Neuropsychological Assessment Second Edition (NEPSY-II) Sub Test:Fingertip tapping repetitions scaled score Minimum possible score: 1 Maximum possible score: 19 A higher score is indicative of a better outcome.
  • Fingertip Tapping Sequences Scaled Score [ Time Frame: At 5 years corrected age ]
    Developmental Neuropsychological Assessment Second Edition (NEPSY-II) Sub Test: fingertip tapping sequences scaled score Minimum possible score: 1 Maximum possible score: 19 A higher score indicates a better outcome.
  • Design Copy Process Total Scaled Score [ Time Frame: At 5 years corrected age ]
    Developmental Neuropsychological Assessment Second Edition (NEPSY-II) Sub Test: Design Copy Process Total Scaled Score Minimum possible score: 1 Maximum possible score: 19 A higher score indicates a better outcome.
  • Word Reading Standard Score [ Time Frame: At 5 years chronological age ]
    Weschler Individual Achievement Test (WIAT-II Abbreviated) to assess the academic skills of the child: Word Reading standard score Minimum possible score: 45 Maximum possible score: 145 Note: Scale ranges represent estimates that are very likely to be accurate but which will be verified after access to the physical assessment booklets is restored. The current health situation prohibits the research team from verifying this information at the moment. A higher score indicates a better outcome.
  • Numerical Operations Standard Score [ Time Frame: At 5 years chronological age ]
    Weschler Individual Achievement Test (WIAT-II Abbreviated) to Assess the Academic Skills of the Child: Numerical Operations standard score Minimum possible score: 45 Maximum possible score: 145 Note: Scale ranges represent estimates that are very likely to be accurate but which will be verified after access to the physical assessment booklets is restored. The current health situation prohibits the research team from verifying this information at the moment. A higher score indicates a better outcome.
  • Spelling Standard Score [ Time Frame: At 5 years chronological age ]
    Weschler Individual Achievement Test (WIAT-II Abbreviated) to Assess the Academic Skills of the Child: Spelling standard score Minimum possible score: 45 Maximum possible score: 145 A higher score indicates a better outcome. Note: Scale ranges represent estimates that are very likely to be accurate but which will be verified after access to the physical assessment booklets is restored. The current health situation prohibits the research team from verifying this information at the moment.
  • Numbers Total Scaled Score [ Time Frame: At 5 years chronological age ]
    Children's Memory Scale (CMS):Numbers Total scaled score Minimum possible score: 1 Maximum possible score: 19 A higher score indicates a better outcome.
  • Word Lists 1 (Learning) Scaled Score [ Time Frame: At 5 years chronological age ]
    Children's Memory Scale (CMS): Word Lists 1 (learning) scaled score Minimum possible score: 1 Maximum possible score: 19 A higher score indicates a better outcome.
  • Memory and Learning Word Lists II (Delayed) Scaled Score [ Time Frame: At 5 years chronological age ]
    Children's Memory Scale (CMS): Memory and learning Word Lists II (delayed) scaled score Minimum possible score: 1 Maximum possible score: 19 A higher score indicates a better outcome.
  • The Global Executive Composite (GEC) of the Behaviour Rating of Executive Function [ Time Frame: At 5 years chronological age ]
    Full title: The Global Executive Composite (GEC) of the Behaviour Rating of Executive Function Preschool Version Parent Form (BRIEF-P) to measure behavioural executive abilities. Minimum possible score: 40 Maximum possible score: 110 Note: Scale ranges represent estimates that are very likely to be accurate but which will be verified after access to the physical assessment booklets is restored. The current health situation prohibits the research team from verifying this information at the moment. A higher score indicates a worse outcome.
  • The Global Adaptive Composite (GAC) of the Adaptive Behavior Assessment System [ Time Frame: At 5 years chronological age ]
    Full title: The Global Adaptive Composite (GAC) of the Adaptive Behavior Assessment System - 2nd edition (ABAS-II) to measure the child's adaptive behavior. Minimum possible score: 45 Maximum possible score: 145 A higher score indicates a better outcome. Note: Scale ranges represent estimates that are very likely to be accurate but which will be verified after access to the physical assessment booklets is restored. The current health situation prohibits the research team from verifying this information at the moment.
  • Total Problems Score [ Time Frame: At 5 years chronological age ]
    Child Behaviour Checklist Caregiver Questionnaire (CBCL): Total Problems Score to measure behavioural problems Minimum possible score: 40 Maximum possible score: 100 A higher score indicates a worse outcome. Note: Scale ranges represent estimates that are very likely to be accurate but which will be verified after access to the physical assessment booklets is restored. The current health situation prohibits the research team from verifying this information at the moment.
  • Internalising Problems T Score [ Time Frame: At 5 years chronological age ]
    Child Behaviour Checklist Caregiver Questionnaire (CBCL): CBCL internalising problems T score Minimum possible score: 40 Maximum possible score: 100 A higher score indicates a worse outcome. Note: Scale ranges represent estimates that are very likely to be accurate but which will be verified after access to the physical assessment booklets is restored. The current health situation prohibits the research team from verifying this information at the moment.
  • Externalising Problems T Score [ Time Frame: At 5 years chronological age ]
    Child Behaviour Checklist Caregiver Questionnaire (CBCL): externalising problems T score Minimum possible score: 40 Maximum possible score: 100 A higher score indicates a worse outcome. Note: Scale ranges represent estimates that are very likely to be accurate but which will be verified after access to the physical assessment booklets is restored. The current health situation prohibits the research team from verifying this information at the moment.
  • Speech or Language Interventions [ Time Frame: At 5 years chronological age ]
    Speech or language issues/interventions. These variables will be summarised using descriptive statistics by treatment arm only. No treatment effect or confidence intervals will be calculated.
  • Psychomotor Interventions [ Time Frame: At 5 years chronological age ]
    Psychomotor issues/interventions. These variables will be summarised using descriptive statistics by treatment arm only. No treatment effect or confidence intervals will be calculated.
  • Number of Participants With Global Developmental Delay [ Time Frame: At 5 years chronological age ]
    Child has global developmental delay. These variables will be summarised using descriptive statistics by treatment arm only. No treatment effect or confidence intervals will be calculated.
  • Number of Participants With Attention Deficit Hyperactivity Disorder [ Time Frame: At 5 years chronological age ]
    Child has been diagnosed with Attention Deficit Hyperactivity Disorder. These variables will be summarised using descriptive statistics by treatment arm only. No treatment effect or confidence intervals will be calculated.
  • Number of Participants With Autism Spectrum Disorder [ Time Frame: At 5 years chronological age ]
    Child has been diagnosis with Autism Spectrum Disorder. These variables will be summarised using descriptive statistics by treatment arm only. No treatment effect or confidence intervals will be calculated.
  • Number of Participants With a Hearing Abnormality [ Time Frame: At 5 years chronological age ]
    Child has a hearing abnormality. These variables will be summarised using descriptive statistics by treatment arm only. No treatment effect or confidence intervals will be calculated.
  • Number of Participants With a Visual Defect in Either Eye [ Time Frame: At 5 years chronological age ]
    Child has a visual defect in either eye. These variables will be summarised using descriptive statistics by treatment arm only. No treatment effect or confidence intervals will be calculated.
  • Number of Participants With a Hearing Aid [ Time Frame: At 5 years chronological age ]
    Child has a hearing aid. These variables will be summarised using descriptive statistics by treatment arm only. No treatment effect or confidence intervals will be calculated.
  • Number of Participants Who Are Legally Blind [ Time Frame: At 5 years chronological age ]
    Child is legally blind. These variables will be summarised using descriptive statistics by treatment arm only. No treatment effect or confidence intervals will be calculated.
  • Number of Participants Who Have Cerebral Palsy [ Time Frame: At 5 years chronological age ]
    Child has cerebral palsy. These variables will be summarised using descriptive statistics by treatment arm only. No treatment effect or confidence intervals will be calculated.
  • Parents' Awareness of Group Allocation [ Time Frame: At 5 years chronological age ]
    Whether or not a parent is aware of which treatment group their child was allocated to. This variable will be summarised using descriptive statistics by treatment arm only. No treatment effect or confidence intervals will be calculated.
  • Awareness of Group Allocation by Psychologist [ Time Frame: At 5 years chronological age ]
    These variables will be summarised using descriptive statistics by treatment arm only. No treatment effect or confidence intervals will be calculated.
  • Awareness of Group Allocation by Pediatrician [ Time Frame: At 5 years chronological age ]
Original Secondary Outcome Measures  ICMJE
 (submitted: September 19, 2008)
Bayley neurodevelopmental scale. Also, frequency and characteristics of apnea in the post-operative period. [ Time Frame: At 2 years corrected age. ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Multi-site Randomized Controlled Trial Comparing Regional and General Anesthesia for Effects on Neurodevelopmental Outcome and Apnea in Infants
Official Title  ICMJE A Multi-site Randomised Controlled Trial Comparing Regional and General Anaesthesia for Effects on Neurodevelopmental Outcome and Apnoea in Infants
Brief Summary The primary purpose of the GAS study is to determine whether different types of anesthesia (Regional versus General) given to 720 infants undergoing inguinal hernia repair results in equivalent neurodevelopmental outcomes. The study also aims to describe the incidence of apnea in the post-operative period after both regional and general anesthesia for inguinal hernia repair in infants. This study is important as it will provide the greatest evidence for safety or toxicity of general anesthesia for human infants.
Detailed Description

This is a prospective, observer blind, multi-site, randomized, controlled, equivalence trial. The general anesthesia group will receive sevoflurane (intervention drug) for induction and maintenance of general anesthesia, dose up to 8% inspired for duration of procedure plus bupivacaine local anesthetic blockade (up to 2.5 mg per kg) administered via caudal or ilioinguinal nerve block. The airway can be maintained with a face mask, laryngeal mask or endotracheal tube, with or without neuromuscular blocking agents.

The regional group will have no sedative agent. The regional blockade may be with spinal alone, spinal block with caudal block, spinal with ilioinguinal block or caudal alone. The maximum dose of 2.5 mg per kg of bupivacaine can be used.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Inguinal Hernia
Intervention  ICMJE
  • Drug: Regional Anesthesia
    Up to 2.5 mg/kg bupivacaine administered by caudal or subarachnoid routes or both caudal and subarachnoid or subarachnoid and ilioinguinal nerve blockade. Single shot.
    Other Name: Spinal Anesthesia.
  • Drug: General Anesthesia
    Sevoflurane for induction and maintenance of general anesthesia, dose up to 8% inspired for duration of procedure plus bupivacaine local anesthetic blockade (up to 2.5 mg/kg) administered via caudal or ilioinguinal nerve block.
    Other Name: General Anesthesia.
Study Arms  ICMJE
  • Active Comparator: 1
    Regional Anesthesia
    Intervention: Drug: Regional Anesthesia
  • Active Comparator: 2
    General Anesthesia
    Intervention: Drug: General Anesthesia
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 16, 2020)
643
Original Estimated Enrollment  ICMJE
 (submitted: September 19, 2008)
660
Actual Study Completion Date  ICMJE June 30, 2018
Actual Primary Completion Date June 30, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Any infant scheduled for unilateral or bilateral inguinal hernia repair (with or without circumcision)
  • Any infant whose gestational age is 26 weeks or more (GA = 182 days)
  • Any infant whose post-menstrual age is up to 60 weeks (PMA = 426 days)

Exclusion Criteria:

  • Any child older than 60 weeks post-menstrual age
  • Any child born less than 26 weeks gestation
  • Any contraindication to general or spinal/caudal anesthesia (for example: neuromuscular disorder or coagulopathy)
  • Pre-operative ventilation immediately prior to surgery
  • Congenital heart disease that has required ongoing pharmacotherapy
  • Known chromosomal abnormality or any other known acquired or congenital abnormalities (apart from prematurity) which are likely to affect development
  • Children where follow-up would be difficult for geographic or social reasons
  • Families where English is not the primary language spoken at home
  • Known neurological injury such as cystic periventricular leukomalacia (PVL), or grade 3 or 4 intra ventricular hemorrhage (ICH) (+/- post hemorrhage ventricular dilation)
  • Previous exposure to volatile anesthesia or benzodiazepines as a neonate or in the third trimester in utero.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 60 Weeks   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Canada,   Italy,   Netherlands,   New Zealand,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00756600
Other Study ID Numbers  ICMJE 06-07-0320
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Mary Ellen McCann, Boston Children's Hospital
Study Sponsor  ICMJE Boston Children's Hospital
Collaborators  ICMJE
  • Royal Children's Hospital
  • Royal Hospital for Sick Children
  • Murdoch Childrens Research Institute
  • Food and Drug Administration (FDA)
Investigators  ICMJE
Principal Investigator: Andrew Davidson, MD Royal Children's Hospital, Victoria, Australia
Principal Investigator: Mary Ellen McCann, MD Children's Hospital Boston, United States of America
Principal Investigator: Neil Morton, MD Royal Hospital for Sick Children, Glasgow, United Kingdom
PRS Account Boston Children's Hospital
Verification Date April 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP