Please note the ANZCTR will be unattended from Friday 24 December 2021 for the holidays. The Registry will re-open on Monday 17 January 2022. Submissions and updates will not be processed during that time.

For new and updated trial submissions, we are processing trials as quickly as possible and appreciate your patience. We recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00756600




Registration number
NCT00756600
Ethics application status
Date submitted
18/09/2008
Date registered
22/09/2008
Date last updated
29/04/2020

Titles & IDs
Public title
A Multi-site Randomized Controlled Trial Comparing Regional and General Anesthesia for Effects on Neurodevelopmental Outcome and Apnea in Infants
Scientific title
A Multi-site Randomised Controlled Trial Comparing Regional and General Anaesthesia for Effects on Neurodevelopmental Outcome and Apnoea in Infants
Secondary ID [1] 0 0
06-07-0320
Universal Trial Number (UTN)
Trial acronym
GAS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Inguinal Hernia 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Regional Anesthesia
Treatment: Drugs - General Anesthesia

Active Comparator: 1 - Regional Anesthesia

Active Comparator: 2 - General Anesthesia


Treatment: Drugs: 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.

Treatment: Drugs: 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.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Full Scale IQ Score - 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.
Timepoint [1] 0 0
At 5 years chronological age
Secondary outcome [1] 0 0
Verbal IQ - 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.
Timepoint [1] 0 0
At 5 years corrected age.
Secondary outcome [2] 0 0
Performance IQ - 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.
Timepoint [2] 0 0
At 5 years corrected age
Secondary outcome [3] 0 0
Processing Speed Quotient - 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.
Timepoint [3] 0 0
At 5 years corrected age
Secondary outcome [4] 0 0
Sentence Repetition Scaled Score - 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.
Timepoint [4] 0 0
At 5 years chronological age
Secondary outcome [5] 0 0
Auditory Attention Combined Scaled Score - 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.
Timepoint [5] 0 0
At 5 years corrected age
Secondary outcome [6] 0 0
Statue Scaled Score - 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.
Timepoint [6] 0 0
At 5 years corrected age
Secondary outcome [7] 0 0
Inhibition Combined Scaled Score - 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.
Timepoint [7] 0 0
At 5 years corrected age
Secondary outcome [8] 0 0
Word Generation Scaled Score - 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.
Timepoint [8] 0 0
At 5 years corrected age
Secondary outcome [9] 0 0
Affect Recognition Scaled Score - 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.
Timepoint [9] 0 0
At 5 years corrected age
Secondary outcome [10] 0 0
Memory for Names and Memory for Names Delay - 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.
Timepoint [10] 0 0
At 5 years corrected age
Secondary outcome [11] 0 0
Theory of Mind Scaled Score - 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.
Timepoint [11] 0 0
At 5 years corrected age
Secondary outcome [12] 0 0
Speeded Naming Combined Scaled Score - 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.
Timepoint [12] 0 0
At 5 years corrected age
Secondary outcome [13] 0 0
Fingertip Tapping Repetitions Scaled Score - 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.
Timepoint [13] 0 0
At 5 years corrected age
Secondary outcome [14] 0 0
Fingertip Tapping Sequences Scaled Score - 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.
Timepoint [14] 0 0
At 5 years corrected age
Secondary outcome [15] 0 0
Design Copy Process Total Scaled Score - 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.
Timepoint [15] 0 0
At 5 years corrected age
Secondary outcome [16] 0 0
Word Reading Standard Score - 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.
Timepoint [16] 0 0
At 5 years chronological age
Secondary outcome [17] 0 0
Numerical Operations Standard Score - 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.
Timepoint [17] 0 0
At 5 years chronological age
Secondary outcome [18] 0 0
Spelling Standard Score - 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.
Timepoint [18] 0 0
At 5 years chronological age
Secondary outcome [19] 0 0
Numbers Total Scaled Score - Children's Memory Scale (CMS):Numbers Total scaled score
Minimum possible score: 1 Maximum possible score: 19
A higher score indicates a better outcome.
Timepoint [19] 0 0
At 5 years chronological age
Secondary outcome [20] 0 0
Word Lists 1 (Learning) Scaled Score - 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.
Timepoint [20] 0 0
At 5 years chronological age
Secondary outcome [21] 0 0
Memory and Learning Word Lists II (Delayed) Scaled Score - 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.
Timepoint [21] 0 0
At 5 years chronological age
Secondary outcome [22] 0 0
The Global Executive Composite (GEC) of the Behaviour Rating of Executive Function - 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.
Timepoint [22] 0 0
At 5 years chronological age
Secondary outcome [23] 0 0
The Global Adaptive Composite (GAC) of the Adaptive Behavior Assessment System - 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.
Timepoint [23] 0 0
At 5 years chronological age
Secondary outcome [24] 0 0
Total Problems Score - 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.
Timepoint [24] 0 0
At 5 years chronological age
Secondary outcome [25] 0 0
Internalising Problems T Score - 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.
Timepoint [25] 0 0
At 5 years chronological age
Secondary outcome [26] 0 0
Externalising Problems T Score - 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.
Timepoint [26] 0 0
At 5 years chronological age
Secondary outcome [27] 0 0
Speech or Language Interventions - 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.
Timepoint [27] 0 0
At 5 years chronological age
Secondary outcome [28] 0 0
Psychomotor Interventions - Psychomotor issues/interventions. These variables will be summarised using descriptive statistics by treatment arm only. No treatment effect or confidence intervals will be calculated.
Timepoint [28] 0 0
At 5 years chronological age
Secondary outcome [29] 0 0
Number of Participants With Global Developmental Delay - 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.
Timepoint [29] 0 0
At 5 years chronological age
Secondary outcome [30] 0 0
Number of Participants With Attention Deficit Hyperactivity Disorder - 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.
Timepoint [30] 0 0
At 5 years chronological age
Secondary outcome [31] 0 0
Number of Participants With Autism Spectrum Disorder - 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.
Timepoint [31] 0 0
At 5 years chronological age
Secondary outcome [32] 0 0
Number of Participants With a Hearing Abnormality - 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.
Timepoint [32] 0 0
At 5 years chronological age
Secondary outcome [33] 0 0
Number of Participants With a Visual Defect in Either Eye - 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.
Timepoint [33] 0 0
At 5 years chronological age
Secondary outcome [34] 0 0
Number of Participants With a Hearing Aid - 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.
Timepoint [34] 0 0
At 5 years chronological age
Secondary outcome [35] 0 0
Number of Participants Who Are Legally Blind - 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.
Timepoint [35] 0 0
At 5 years chronological age
Secondary outcome [36] 0 0
Number of Participants Who Have Cerebral Palsy - 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.
Timepoint [36] 0 0
At 5 years chronological age
Secondary outcome [37] 0 0
Parents' Awareness of Group Allocation - 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.
Timepoint [37] 0 0
At 5 years chronological age
Secondary outcome [38] 0 0
Awareness of Group Allocation by Psychologist - These variables will be summarised using descriptive statistics by treatment arm only. No treatment effect or confidence intervals will be calculated.
Timepoint [38] 0 0
At 5 years chronological age
Secondary outcome [39] 0 0
Awareness of Group Allocation by Pediatrician
Timepoint [39] 0 0
At 5 years chronological age

Eligibility
Key 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)
Minimum age
No limit
Maximum age
60 Weeks
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA,VIC,WA
Recruitment hospital [1] 0 0
Adelaide Women's and Children's Hospital - North Adelaide
Recruitment hospital [2] 0 0
Casey Hospital - Berwick
Recruitment hospital [3] 0 0
Monash Medical Centre - Clayton
Recruitment hospital [4] 0 0
Cabrini Hospital - Malvern
Recruitment hospital [5] 0 0
Royal Children's Hospital - Parkville
Recruitment hospital [6] 0 0
Princess Margaret Hospital - Perth
Recruitment postcode(s) [1] 0 0
5006 - North Adelaide
Recruitment postcode(s) [2] 0 0
3806 - Berwick
Recruitment postcode(s) [3] 0 0
3165 - Clayton
Recruitment postcode(s) [4] 0 0
3144 - Malvern
Recruitment postcode(s) [5] 0 0
3052 - Parkville
Recruitment postcode(s) [6] 0 0
6008 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Colorado
Country [2] 0 0
United States of America
State/province [2] 0 0
Illinois
Country [3] 0 0
United States of America
State/province [3] 0 0
Iowa
Country [4] 0 0
United States of America
State/province [4] 0 0
Massachusetts
Country [5] 0 0
United States of America
State/province [5] 0 0
New Hampshire
Country [6] 0 0
United States of America
State/province [6] 0 0
Pennsylvania
Country [7] 0 0
United States of America
State/province [7] 0 0
Tennessee
Country [8] 0 0
United States of America
State/province [8] 0 0
Texas
Country [9] 0 0
United States of America
State/province [9] 0 0
Vermont
Country [10] 0 0
United States of America
State/province [10] 0 0
Washington
Country [11] 0 0
Canada
State/province [11] 0 0
Quebec
Country [12] 0 0
Italy
State/province [12] 0 0
Bergamo
Country [13] 0 0
Italy
State/province [13] 0 0
Genoa
Country [14] 0 0
Italy
State/province [14] 0 0
Milano
Country [15] 0 0
Netherlands
State/province [15] 0 0
Groningen
Country [16] 0 0
Netherlands
State/province [16] 0 0
Utrecht
Country [17] 0 0
New Zealand
State/province [17] 0 0
Auckland
Country [18] 0 0
United Kingdom
State/province [18] 0 0
Belfast
Country [19] 0 0
United Kingdom
State/province [19] 0 0
Birmingham
Country [20] 0 0
United Kingdom
State/province [20] 0 0
Bristol
Country [21] 0 0
United Kingdom
State/province [21] 0 0
Glasgow
Country [22] 0 0
United Kingdom
State/province [22] 0 0
Liverpool
Country [23] 0 0
United Kingdom
State/province [23] 0 0
Sheffield

Funding & Sponsors
Primary sponsor type
Other
Name
Boston Children's Hospital
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Royal Children's Hospital
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Royal Hospital for Sick Children
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
Murdoch Childrens Research Institute
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Government body
Name [4] 0 0
Food and Drug Administration (FDA)
Address [4] 0 0
Country [4] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT00756600
Trial related presentations / publications
Davidson A, McCann ME, Morton N. Anesthesia neurotoxicity in neonates: the need for clinical research. Anesth Analg. 2007 Sep;105(3):881-2.
Public notes

Contacts
Principal investigator
Name 0 0
Andrew Davidson, MD
Address 0 0
Royal Children's Hospital, Victoria, Australia
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications