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

NCT00756600 | Completed Phase 4 Results DMC FDA Drug

• 1 other identifier: 06-07-0320
• Study Type: interventional
• Target: 643
• Locations: 7 countries
• Sites: 30

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.

Conditions

Inguinal Hernia

Keywords

Infants; scheduled; unilateral; bilateral; repair

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (39)

• Verbal IQ

  At 5 years corrected age.

• Performance IQ

  At 5 years corrected age

• Processing Speed Quotient

  At 5 years corrected age

• Sentence Repetition Scaled Score

  At 5 years chronological age

• Auditory Attention Combined Scaled Score

  At 5 years corrected age

Study Arms (2)

1

ACTIVE COMPARATOR

Regional Anesthesia

Drug: Regional Anesthesia

2

ACTIVE COMPARATOR

General Anesthesia

Drug: General Anesthesia

Interventions

Regional Anesthesia 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.

Also known as: Spinal Anesthesia.

1

General Anesthesia 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.

Also known as: General Anesthesia.

2

Eligibility Criteria

• Age: Up to 60 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Boston Children's Hospital: lead
• Royal Children's Hospital: collaborator
• Royal Hospital for Sick Children: collaborator
• Murdoch Childrens Research Institute: collaborator
• Food and Drug Administration (FDA): collaborator

Study Sites (30)

The Children's Hospital Denver

Aurora, Colorado, 80045, United States

Location

Children's Memorial Hospital

Chicago, Illinois, 60614, United States

Location

The University of Iowa Hospital

Iowa City, Iowa, 52242, United States

Location

Children's Hospital Boston

Boston, Massachusetts, 02115, United States

Location

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Vanderbilt Children's Hospital

Nashville, Tennessee, 37212, United States

Location

Children's Medical Center of Dallas

Dallas, Texas, 75235, United States

Location

Vermont Children's Hospital at Fletcher Allen Health Care

Burlington, Vermont, 05401, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Adelaide Women's and Children's Hospital

North Adelaide, South Australia, 5006, Australia

Location

Casey Hospital

Berwick, Victoria, 3806, Australia

Location

Monash Medical Centre

Clayton, Victoria, 3165, Australia

Location

Cabrini Hospital

Malvern, Victoria, 3144, Australia

Location

Royal Children's Hospital

Parkville, Victoria, 3052, Australia

Location

Princess Margaret Hospital

Perth, Western Australia, 6008, Australia

Location

Montreal Children's Hospital

Montreal, Quebec, H3H 1P3, Canada

Location

Centre Hospitalier Universitaire Sainte-Justine

Montreal, Quebec, H3T 1C5, Canada

Location

Ospedali Riuniti Di Bergamo

Bergamo, 24100, Italy

Location

G. Gaslini Children's Hospital

Genoa, 16147, Italy

Location

'Vitore Buzzi' Children's Hospital

Milan, 20100, Italy

Location

Universitair Medisch Centrum Groningen

Groningen, 9700 RB, Netherlands

Location

Wilhelmina Children's Hospital; University Medical Centre Utrecht

Utrecht, Netherlands

Location

Starship Children's Health

Auckland, New Zealand

Location

Royal Belfast Hospital for Sick Children

Belfast, BT12 6BE, United Kingdom

Location

Birmingham Children's Hospital

Birmingham, B4 6NH, United Kingdom

Location

Bristol Royal Hospital for Children

Bristol, BS2 8BJ, United Kingdom

Location

Royal Hospital for Sick Children

Glasgow, G3 8SJ, United Kingdom

Location

Royal Liverpool Children's Hospital

Liverpool, L12 2APS, United Kingdom

Location

Sheffield Children's Hospital

Sheffield, S10 2TS, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 17717261 BACKGROUND

• 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.

  PMID: 30782342 DERIVED

• 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.

  PMID: 26507180 DERIVED

MeSH Terms

Conditions

Hernia, Inguinal

Interventions

Anesthesia, Conduction; Anesthesia, Spinal; Anesthesia, General

Condition Hierarchy (Ancestors)

Hernia, Abdominal; Hernia; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Anesthesia; Anesthesia and Analgesia

Results Point of Contact

• Title: Dr Mary Ellen McCann
• Organization: Boston Children's Hospital Anesthesia Foundation

mary.mccann@childrens.harvard.edu

6173557737

Study Officials

• Andrew Davidson, MD

  Royal Children's Hospital, Victoria, Australia

  PRINCIPAL INVESTIGATOR

• Mary Ellen McCann, MD

  Children's Hospital Boston, United States of America

  PRINCIPAL INVESTIGATOR

• Neil Morton, MD

  Royal Hospital for Sick Children, Glasgow, United Kingdom

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: September 18, 2008
• First Posted: September 22, 2008
• Study Start: October 23, 2006
• Primary Completion: June 30, 2018
• Study Completion: June 30, 2018
• Last Updated: April 29, 2020
• Results First Posted: April 29, 2020

Record last verified: 2020-04

Locations

CA (2); US (10); IT (3); NL (2); AU (6); NZ (1); GB (6)