Clinical trial NCT00756600: A Multi-site Randomized Controlled Trial Comparing Regional and General Anesthesia for Effects on Neurodevelopmental Outcome and Apnea in Infants
Official title: A Multi-site Randomised Controlled Trial Comparing Regional and General Anaesthesia for Effects on Neurodevelopmental Outcome and Apnoea in Infants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Inguinal Hernia
Keywords: Infants
scheduled
unilateral
bilateral
repair
Lead sponsor: Boston Children's Hospital
Sponsor class: OTHER
Collaborators: name: Royal Children's Hospital
name: Royal Hospital for Sick Children
name: Murdoch Childrens Research Institute
name: Food and Drug Administration (FDA)
First posted: 2008-09-22
Enrollment: 643
Sex: ALL
Maximum age (years): 60
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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.

Primary outcomes:
measure: Full Scale IQ Score
timeFrame: At 5 years chronological age
Secondary outcomes:
measure: Verbal IQ
timeFrame: At 5 years corrected age.
measure: Performance IQ
timeFrame: At 5 years corrected age
measure: Processing Speed Quotient
timeFrame: At 5 years corrected age
measure: Sentence Repetition Scaled Score
timeFrame: At 5 years chronological age
measure: Auditory Attention Combined Scaled Score
timeFrame: At 5 years corrected age
measure: Statue Scaled Score
timeFrame: At 5 years corrected age
measure: Inhibition Combined Scaled Score
timeFrame: At 5 years corrected age
measure: Word Generation Scaled Score
timeFrame: At 5 years corrected age
measure: Affect Recognition Scaled Score
timeFrame: At 5 years corrected age
measure: Memory for Names and Memory for Names Delay
timeFrame: At 5 years corrected age
measure: Theory of Mind Scaled Score
timeFrame: At 5 years corrected age
measure: Speeded Naming Combined Scaled Score
timeFrame: At 5 years corrected age
measure: Fingertip Tapping Repetitions Scaled Score
timeFrame: At 5 years corrected age
measure: Fingertip Tapping Sequences Scaled Score
timeFrame: At 5 years corrected age
measure: Design Copy Process Total Scaled Score
timeFrame: At 5 years corrected age
measure: Word Reading Standard Score
timeFrame: At 5 years chronological age
measure: Numerical Operations Standard Score
timeFrame: At 5 years chronological age
measure: Spelling Standard Score
timeFrame: At 5 years chronological age
measure: Numbers Total Scaled Score
timeFrame: At 5 years chronological age
measure: Word Lists 1 (Learning) Scaled Score
timeFrame: At 5 years chronological age
measure: Memory and Learning Word Lists II (Delayed) Scaled Score
timeFrame: At 5 years chronological age
measure: The Global Executive Composite (GEC) of the Behaviour Rating of Executive Function
timeFrame: At 5 years chronological age
measure: The Global Adaptive Composite (GAC) of the Adaptive Behavior Assessment System
timeFrame: At 5 years chronological age
measure: Total Problems Score
timeFrame: At 5 years chronological age
measure: Internalising Problems T Score
timeFrame: At 5 years chronological age
measure: Externalising Problems T Score
timeFrame: At 5 years chronological age
measure: Speech or Language Interventions
timeFrame: At 5 years chronological age
measure: Psychomotor Interventions
timeFrame: At 5 years chronological age
measure: Number of Participants With Global Developmental Delay
timeFrame: At 5 years chronological age
measure: Number of Participants With Attention Deficit Hyperactivity Disorder
timeFrame: At 5 years chronological age
measure: Number of Participants With Autism Spectrum Disorder
timeFrame: At 5 years chronological age
measure: Number of Participants With a Hearing Abnormality
timeFrame: At 5 years chronological age
measure: Number of Participants With a Visual Defect in Either Eye
timeFrame: At 5 years chronological age
measure: Number of Participants With a Hearing Aid
timeFrame: At 5 years chronological age
measure: Number of Participants Who Are Legally Blind
timeFrame: At 5 years chronological age
measure: Number of Participants Who Have Cerebral Palsy
timeFrame: At 5 years chronological age
measure: Parents' Awareness of Group Allocation
timeFrame: At 5 years chronological age
measure: Awareness of Group Allocation by Psychologist
timeFrame: At 5 years chronological age
measure: Awareness of Group Allocation by Pediatrician
timeFrame: At 5 years chronological age
Other outcomes:
Locations:
city: Aurora
country: United States
facility: The Children's Hospital Denver
state: Colorado
city: Chicago
country: United States
facility: Children's Memorial Hospital
state: Illinois
city: Iowa City
country: United States
facility: The University of Iowa Hospital
state: Iowa
city: Boston
country: United States
facility: Children's Hospital Boston
state: Massachusetts
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt Children's Hospital
state: Tennessee
city: Dallas
country: United States
facility: Children's Medical Center of Dallas
state: Texas
city: Burlington
country: United States
facility: Vermont Children's Hospital at Fletcher Allen Health Care
state: Vermont
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: North Adelaide
country: Australia
facility: Adelaide Women's and Children's Hospital
state: South Australia
city: Berwick
country: Australia
facility: Casey Hospital
state: Victoria
city: Clayton
country: Australia
facility: Monash Medical Centre
state: Victoria
city: Malvern
country: Australia
facility: Cabrini Hospital
state: Victoria
city: Parkville
country: Australia
facility: Royal Children's Hospital
state: Victoria
city: Perth
country: Australia
facility: Princess Margaret Hospital
state: Western Australia
city: Montreal
country: Canada
facility: Montreal Children's Hospital
state: Quebec
city: Montréal
country: Canada
facility: Centre Hospitalier Universitaire Sainte-Justine
state: Quebec
city: Bergamo
country: Italy
facility: Ospedali Riuniti Di Bergamo
city: Genoa
country: Italy
facility: G. Gaslini Children's Hospital
city: Milano
country: Italy
facility: 'Vitore Buzzi' Children's Hospital
city: Groningen
country: Netherlands
facility: Universitair Medisch Centrum Groningen
city: Utrecht
country: Netherlands
facility: Wilhelmina Children's Hospital; University Medical Centre Utrecht
city: Auckland
country: New Zealand
facility: Starship Children's Health
city: Belfast
country: United Kingdom
facility: Royal Belfast Hospital for Sick Children
city: Birmingham
country: United Kingdom
facility: Birmingham Children's Hospital
city: Bristol
country: United Kingdom
facility: Bristol Royal Hospital for Children
city: Glasgow
country: United Kingdom
facility: Royal Hospital for Sick Children
city: Liverpool
country: United Kingdom
facility: Royal Liverpool Children's Hospital
city: Sheffield
country: United Kingdom
facility: Sheffield Children's Hospital
Study officials:
affiliation: Royal Children's Hospital, Victoria, Australia
name: Andrew Davidson, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Hospital Boston, United States of America
name: Mary Ellen McCann, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Royal Hospital for Sick Children, Glasgow, United Kingdom
name: Neil Morton, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Davidson A, McCann ME, Morton N. Anesthesia neurotoxicity in neonates: the need for clinical research. Anesth Analg. 2007 Sep;105(3):881-2. doi: 10.1213/01.ane.0000269692.57331.48. No abstract available.
citation: 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.
citation: 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.