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

NCT ID: NCT00756600

Last Updated: 2020-04-29

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

643 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-10-23

Study Completion Date

2018-06-30

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.

Conditions

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Inguinal Hernia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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1

Regional Anesthesia

Group Type ACTIVE_COMPARATOR

Regional Anesthesia

Intervention Type DRUG

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.

2

General Anesthesia

Group Type ACTIVE_COMPARATOR

General Anesthesia

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type 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.

Intervention Type DRUG

Other Intervention Names

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Spinal Anesthesia. General Anesthesia.

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.
Maximum Eligible Age

60 Weeks

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Royal Children's Hospital

OTHER

Sponsor Role collaborator

Royal Hospital for Sick Children

OTHER

Sponsor Role collaborator

Murdoch Childrens Research Institute

OTHER

Sponsor Role collaborator

Food and Drug Administration (FDA)

FED

Sponsor Role collaborator

Boston Children's Hospital

OTHER

Sponsor Role lead

Responsible Party

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Mary Ellen McCann

MD

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Andrew Davidson, MD

Role: PRINCIPAL_INVESTIGATOR

Royal Children's Hospital, Victoria, Australia

Mary Ellen McCann, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital Boston, United States of America

Neil Morton, MD

Role: PRINCIPAL_INVESTIGATOR

Royal Hospital for Sick Children, Glasgow, United Kingdom

Locations

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The Children's Hospital Denver

Aurora, Colorado, United States

Site Status

Children's Memorial Hospital

Chicago, Illinois, United States

Site Status

The University of Iowa Hospital

Iowa City, Iowa, United States

Site Status

Children's Hospital Boston

Boston, Massachusetts, United States

Site Status

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, United States

Site Status

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Vanderbilt Children's Hospital

Nashville, Tennessee, United States

Site Status

Children's Medical Center of Dallas

Dallas, Texas, United States

Site Status

Vermont Children's Hospital at Fletcher Allen Health Care

Burlington, Vermont, United States

Site Status

Seattle Children's Hospital

Seattle, Washington, United States

Site Status

Adelaide Women's and Children's Hospital

North Adelaide, South Australia, Australia

Site Status

Casey Hospital

Berwick, Victoria, Australia

Site Status

Monash Medical Centre

Clayton, Victoria, Australia

Site Status

Cabrini Hospital

Malvern, Victoria, Australia

Site Status

Royal Children's Hospital

Parkville, Victoria, Australia

Site Status

Princess Margaret Hospital

Perth, Western Australia, Australia

Site Status

Montreal Children's Hospital

Montreal, Quebec, Canada

Site Status

Centre Hospitalier Universitaire Sainte-Justine

Montreal, Quebec, Canada

Site Status

Ospedali Riuniti Di Bergamo

Bergamo, , Italy

Site Status

G. Gaslini Children's Hospital

Genoa, , Italy

Site Status

'Vitore Buzzi' Children's Hospital

Milan, , Italy

Site Status

Universitair Medisch Centrum Groningen

Groningen, , Netherlands

Site Status

Wilhelmina Children's Hospital; University Medical Centre Utrecht

Utrecht, , Netherlands

Site Status

Starship Children's Health

Auckland, , New Zealand

Site Status

Royal Belfast Hospital for Sick Children

Belfast, , United Kingdom

Site Status

Birmingham Children's Hospital

Birmingham, , United Kingdom

Site Status

Bristol Royal Hospital for Children

Bristol, , United Kingdom

Site Status

Royal Hospital for Sick Children

Glasgow, , United Kingdom

Site Status

Royal Liverpool Children's Hospital

Liverpool, , United Kingdom

Site Status

Sheffield Children's Hospital

Sheffield, , United Kingdom

Site Status

Countries

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United States Australia Canada Italy Netherlands New Zealand United Kingdom

References

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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.

Reference Type BACKGROUND
PMID: 17717261 (View on PubMed)

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.

Reference Type DERIVED
PMID: 30782342 (View on PubMed)

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.

Reference Type DERIVED
PMID: 26507180 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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06-07-0320

Identifier Type: -

Identifier Source: org_study_id

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