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

Inguinal Hernia Clinical Trial

— GAS  

Official title:

A Multi-site Randomised Controlled Trial Comparing Regional and General Anaesthesia for Effects on Neurodevelopmental Outcome and Apnoea in Infants

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00756600
• Other study ID #: 06-07-0320
• Status: Completed
• Phase: Phase 4
• Start date: October 23, 2006
• Est. completion date: June 30, 2018

Study information

• Verified date: April 2020
• Source: Boston Children’s Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 643
• Est. completion date: June 30, 2018
• Est. primary completion date: June 30, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 60 Weeks

Eligibility

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.

Related Conditions & MeSH terms

• Hernia, Inguinal
• Inguinal Hernia

Intervention

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.
• 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.

Locations

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

Sponsors (5)

Lead Sponsor	Collaborator
Boston Children’s Hospital	Food and Drug Administration (FDA), Murdoch Childrens Research Institute, Royal Children's Hospital, Royal Hospital for Sick Children

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Italy,  Netherlands,  New Zealand,  United Kingdom, 

References & Publications (1)

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	At 5 years chronological age
Secondary	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.	At 5 years corrected age.
Secondary	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.	At 5 years corrected age
Secondary	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.	At 5 years corrected age
Secondary	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.	At 5 years chronological age
Secondary	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.	At 5 years corrected age
Secondary	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.	At 5 years corrected age
Secondary	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.	At 5 years corrected age
Secondary	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.	At 5 years corrected age
Secondary	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.	At 5 years corrected age
Secondary	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.	At 5 years corrected age
Secondary	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.	At 5 years corrected age
Secondary	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.	At 5 years corrected age
Secondary	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.	At 5 years corrected age
Secondary	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.	At 5 years corrected age
Secondary	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.	At 5 years corrected age
Secondary	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.	At 5 years chronological age
Secondary	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.	At 5 years chronological age
Secondary	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.	At 5 years chronological age
Secondary	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.	At 5 years chronological age
Secondary	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.	At 5 years chronological age
Secondary	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.	At 5 years chronological age
Secondary	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.	At 5 years chronological age
Secondary	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.	At 5 years chronological age
Secondary	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.	At 5 years chronological age
Secondary	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.	At 5 years chronological age
Secondary	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.	At 5 years chronological age
Secondary	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.	At 5 years chronological age
Secondary	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.	At 5 years chronological age
Secondary	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.	At 5 years chronological age
Secondary	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.	At 5 years chronological age
Secondary	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.	At 5 years chronological age
Secondary	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.	At 5 years chronological age
Secondary	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.	At 5 years chronological age
Secondary	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.	At 5 years chronological age
Secondary	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.	At 5 years chronological age
Secondary	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.	At 5 years chronological age
Secondary	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.	At 5 years chronological age
Secondary	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.	At 5 years chronological age
Secondary	Awareness of Group Allocation by Pediatrician		At 5 years chronological age