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

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 evaluated by the U.S. Federal Government. Read our disclaimer for details.

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

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Inguinal Hernia	Drug: Regional Anesthesia Drug: General Anesthesia	Phase 4

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 Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	643 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Single (Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	A Multi-site Randomised Controlled Trial Comparing Regional and General Anaesthesia for Effects on Neurodevelopmental Outcome and Apnoea in Infants
Actual Study Start Date :	October 23, 2006
Actual Primary Completion Date :	June 30, 2018
Actual Study Completion Date :	June 30, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hernia

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: 1 Regional Anesthesia	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.
Active Comparator: 2 General 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.

Outcome Measures

Primary Outcome Measures :

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.

Secondary Outcome Measures :

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 ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	up to 60 Weeks (Child)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00756600

Locations

Show 30 study locations

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United States, Colorado
The Children's Hospital Denver
Aurora, Colorado, United States, 80045
United States, Illinois
Children's Memorial Hospital
Chicago, Illinois, United States, 60614
United States, Iowa
The University of Iowa Hospital
Iowa City, Iowa, United States, 52242
United States, Massachusetts
Children's Hospital Boston
Boston, Massachusetts, United States, 02115
United States, New Hampshire
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, United States, 03756
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
United States, Tennessee
Vanderbilt Children's Hospital
Nashville, Tennessee, United States, 37212
United States, Texas
Children's Medical Center of Dallas
Dallas, Texas, United States, 75235
United States, Vermont
Vermont Children's Hospital at Fletcher Allen Health Care
Burlington, Vermont, United States, 05401
United States, Washington
Seattle Children's Hospital
Seattle, Washington, United States, 98105
Australia, South Australia
Adelaide Women's and Children's Hospital
North Adelaide, South Australia, Australia, 5006
Australia, Victoria
Casey Hospital
Berwick, Victoria, Australia, 3806
Monash Medical Centre
Clayton, Victoria, Australia, 3165
Cabrini Hospital
Malvern, Victoria, Australia, 3144
Royal Children's Hospital
Parkville, Victoria, Australia, 3052
Australia, Western Australia
Princess Margaret Hospital
Perth, Western Australia, Australia, 6008
Canada, Quebec
Montreal Children's Hospital
Montreal, Quebec, Canada, H3H 1P3
Centre Hospitalier Universitaire Sainte-Justine
Montréal, Quebec, Canada, H3T 1C5
Italy
Ospedali Riuniti Di Bergamo
Bergamo, Italy, 24100
G. Gaslini Children's Hospital
Genoa, Italy, 16147
'Vitore Buzzi' Children's Hospital
Milano, Italy, 20100
Netherlands
Universitair Medisch Centrum Groningen
Groningen, Netherlands, 9700 RB
Wilhelmina Children's Hospital; University Medical Centre Utrecht
Utrecht, Netherlands
New Zealand
Starship Children's Health
Auckland, New Zealand
United Kingdom
Royal Belfast Hospital for Sick Children
Belfast, United Kingdom, BT12 6BE
Birmingham Children's Hospital
Birmingham, United Kingdom, B4 6NH
Bristol Royal Hospital for Children
Bristol, United Kingdom, BS2 8BJ
Royal Hospital for Sick Children
Glasgow, United Kingdom, G3 8SJ
Royal Liverpool Children's Hospital
Liverpool, United Kingdom, L12 2APS
Sheffield Children's Hospital
Sheffield, United Kingdom, S10 2TS

Sponsors and Collaborators

Boston Children's Hospital

Royal Children's Hospital

Royal Hospital for Sick Children

Murdoch Childrens Research Institute

Food and Drug Administration (FDA)

Investigators

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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

Study Documents (Full-Text)

Documents provided by Mary Ellen McCann, Boston Children's Hospital:

Study Protocol and Statistical Analysis Plan [PDF] February 27, 2020

More Information

Publications:

Davidson A, McCann ME, Morton N. Anesthesia neurotoxicity in neonates: the need for clinical research. Anesth Analg. 2007 Sep;105(3):881-2.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

McCann ME, de Graaff JC, Dorris L, Disma N, Withington D, Bell G, Grobler A, Stargatt R, Hunt RW, Sheppard SJ, Marmor J, Giribaldi G, Bellinger DC, Hartmann PL, Hardy P, Frawley G, Izzo F, von Ungern Sternberg BS, Lynn A, Wilton N, Mueller M, Polaner DM, Absalom AR, Szmuk P, Morton N, Berde C, Soriano S, Davidson AJ; GAS Consortium. Neurodevelopmental outcome at 5 years of age after general anaesthesia or awake-regional anaesthesia in infancy (GAS): an international, multicentre, randomised, controlled equivalence trial. Lancet. 2019 Feb 16;393(10172):664-677. doi: 10.1016/S0140-6736(18)32485-1. Epub 2019 Feb 14. Erratum in: Lancet. 2019 Aug 24;394(10199):638.

Davidson AJ, Disma N, de Graaff JC, Withington DE, Dorris L, Bell G, Stargatt R, Bellinger DC, Schuster T, Arnup SJ, Hardy P, Hunt RW, Takagi MJ, Giribaldi G, Hartmann PL, Salvo I, Morton NS, von Ungern Sternberg BS, Locatelli BG, Wilton N, Lynn A, Thomas JJ, Polaner D, Bagshaw O, Szmuk P, Absalom AR, Frawley G, Berde C, Ormond GD, Marmor J, McCann ME; GAS consortium. Neurodevelopmental outcome at 2 years of age after general anaesthesia and awake-regional anaesthesia in infancy (GAS): an international multicentre, randomised controlled trial. Lancet. 2016 Jan 16;387(10015):239-50. doi: 10.1016/S0140-6736(15)00608-X. Epub 2015 Nov 4. Erratum in: Lancet. 2016 Jan 16;387(10015):228.

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Responsible Party:	Mary Ellen McCann, MD, Boston Children's Hospital
ClinicalTrials.gov Identifier:	NCT00756600
Other Study ID Numbers:	06-07-0320
First Posted:	September 22, 2008 Key Record Dates
Results First Posted:	April 29, 2020
Last Update Posted:	April 29, 2020
Last Verified:	April 2020

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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

Keywords provided by Mary Ellen McCann, Boston Children's Hospital:


Infants scheduled unilateral bilateral repair

Additional relevant MeSH terms:

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Hernia, Inguinal Hernia Pathological Conditions, Anatomical Hernia, Abdominal	Anesthetics Central Nervous System Depressants Physiological Effects of Drugs

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