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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Inguinal Hernia

Intervention / Treatment
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* Drug: Regional Anesthesia
* Drug: General Anesthesia


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Maximum Age: 60 Weeks

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Regional Anesthesia | Drug: Regional Anesthesia<br>* 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.<br>* Other names: Spinal Anesthesia.;|
| Active Comparator: 2<br>General Anesthesia | Drug: General Anesthesia<br>* 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.<br>* Other names: General Anesthesia.;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| Awareness of Group Allocation by Pediatrician |  | At 5 years chronological age | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Infants, scheduled, unilateral, bilateral, repair