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

Phase 4

Completed

Conditions: Inguinal Hernia

Interventions: Drug: General Anesthesia
Drug: Regional Anesthesia

Registration Number: NCT00756600

Lead Sponsor: Boston Children's Hospital

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 643

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
2	General Anesthesia	General Anesthesia
1	Regional Anesthesia	Regional Anesthesia

Primary Outcome Measures

Name	Time	Method
Full Scale IQ Score	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

Name	Time	Method
Verbal IQ	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.
Processing Speed Quotient	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	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	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	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.
Affect Recognition Scaled Score	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	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.
Word Generation Scaled Score	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.
Inhibition Combined Scaled Score	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.
Theory of Mind Scaled Score	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	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	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	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	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.
Performance IQ	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.
Numerical Operations Standard Score	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	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	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	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	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	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.
Word Reading Standard Score	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.
The Global Adaptive Composite (GAC) of the Adaptive Behavior Assessment System	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	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	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	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	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	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	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	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	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	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	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	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	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	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	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	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	At 5 years chronological age

Trial Locations

Locations (30): Dartmouth-Hitchcock Medical Center
🇺🇸
Lebanon, New Hampshire, United States
Children's Hospital of Philadelphia
🇺🇸
Philadelphia, Pennsylvania, United States
Vermont Children's Hospital at Fletcher Allen Health Care
🇺🇸
Burlington, Vermont, United States
Seattle Children's Hospital
🇺🇸
Seattle, Washington, United States
Princess Margaret Hospital
🇦🇺
Perth, Western Australia, Australia
Vanderbilt Children's Hospital
🇺🇸
Nashville, Tennessee, United States
Royal Hospital for Sick Children
🇬🇧
Glasgow, United Kingdom
The Children's Hospital Denver
🇺🇸
Aurora, Colorado, United States
Children's Memorial Hospital
🇺🇸
Chicago, Illinois, United States
Casey Hospital
🇦🇺
Berwick, Victoria, Australia
Children's Medical Center of Dallas
🇺🇸
Dallas, Texas, United States
Universitair Medisch Centrum Groningen
🇳🇱
Groningen, Netherlands
The University of Iowa Hospital
🇺🇸
Iowa City, Iowa, United States
Children's Hospital Boston
🇺🇸
Boston, Massachusetts, United States
Adelaide Women's and Children's Hospital
🇦🇺
North Adelaide, South Australia, Australia
Monash Medical Centre
🇦🇺
Clayton, Victoria, Australia
Cabrini Hospital
🇦🇺
Malvern, Victoria, Australia
Royal Children's Hospital
🇦🇺
Parkville, Victoria, Australia
Ospedali Riuniti Di Bergamo
🇮🇹
Bergamo, Italy
Montreal Children's Hospital
🇨🇦
Montreal, Quebec, Canada
Starship Children's Health
🇳🇿
Auckland, New Zealand
Centre Hospitalier Universitaire Sainte-Justine
🇨🇦
Montréal, Quebec, Canada
G. Gaslini Children's Hospital
🇮🇹
Genoa, Italy
'Vitore Buzzi' Children's Hospital
🇮🇹
Milano, Italy
Wilhelmina Children's Hospital; University Medical Centre Utrecht
🇳🇱
Utrecht, Netherlands
Birmingham Children's Hospital
🇬🇧
Birmingham, United Kingdom
Royal Belfast Hospital for Sick Children
🇬🇧
Belfast, United Kingdom
Bristol Royal Hospital for Children
🇬🇧
Bristol, United Kingdom
Sheffield Children's Hospital
🇬🇧
Sheffield, United Kingdom
Royal Liverpool Children's Hospital
🇬🇧
Liverpool, United Kingdom