A Study to Compare the Long-term Outcomes After Two Different Anaesthetics

Description

There is considerable evidence that most general anaesthetics modulate brain development in animal studies. The impact is greater with longer durations of exposure and in younger animals. There is great controversy over whether or not these animal data are relevant to human clinical scenarios. The changes seen in preclinical studies are greatest with GABA agonists and NMDA antagonists such as volatile anaesthetics (eg sevoflurane), propofol, midazolam, ketamine, and nitrous oxide. There is less evidence for an effect with opioid (such as remifentanil) or with alpha 2 agonists (such as dexmedetomidine). Some, but not all, human cohort studies show an association between exposure to anaesthesia in infancy or early childhood and later changes in cognitive tests, school performance or risk of developing neurodevelopmental disorders. The evidence is weak due to possible confounding. A recent well designed cohort study (the PANDA study) comparing young children that had hernia repair to their siblings found no evidence for a difference in a range of detailed neuropsychological tests. In that study most children were exposed to up to two hours of anaesthesia. The only trial (the GAS trial) has compared children having hernia repair under regional or general anesthesia and has found no evidence for a difference in neurodevelopment when tested at two years of age. The GAS and PANDA studies confirm the animal data that short exposure is unlikely to cause any neurodevelopmental impact. The impact of longer exposures is still unknown. In humans the strongest evidence for an association between surgery and poor neurodevelopmental outcome is in infants having major surgery. However, this is also the group where confounding is most likely. The aim of our study is to see if a new combination of anaesthetic drugs results in a better long-term developmental outcome than the current standard of care for children having surgery lasting at least 2..5 hours. Children will be randomised to receive either a low dose sevoflurane/remifentanil/dexmedetomidine or standard dose sevoflurane anaesthetic. They will receive a neurodevelopmental assessment at 3 years of age to assess global cognitive function.

Study Start Date

August, 10 2017

Estimated Completion Date

April 2022

Interventions

  • Drug: Sevoflurane
  • Drug: Remifentanil
  • Drug: Dexmedetomidine

Study ID

Murdoch Childrens Research Institute -- TREX TRIAL

Status

Recruiting

Trial ID

NCT03089905

Study Type

Interventional

Trial Phase

Phase 3

Enrollment Quota

450

Sponsor

Murdoch Childrens Research Institute

Inclusion Criteria

  • Younger than 2 years (chronological age)
  • Scheduled for surgery that is expected to last at least 2.5 hours (and/or total operating room time is scheduled to be at least 3 hours)
  • Has a legally acceptable representative capable of understanding the informed consent document and providing consent on the participant's behalf.

Exclusion Criteria

  • Known neurologic, chromosomal or congenital anomaly which is likely to be associated with poor neurobehavioural outcome
  • Existing diagnosis of behavioural or neurodevelopmental disability
  • Prematurity (defined as < 36 weeks gestational age at birth)
  • Birth weight less than 2 kg.
  • Congenital cardiac disease requiring surgery
  • Intracranial neurosurgery and intracranial craniofacial surgery (isolated cleft lip is not an exclusion)
  • Previous cumulative exposure to general anaesthesia exceeding 2 hours
  • Planned future cumulative exposure to anaesthesia exceeding 2 hours before the age of 3 years.
  • Any specific contra-indication to any aspect of the protocol
  • Previous adverse reaction to any anaesthetic
  • Circumstances likely to make long term follow-up impossible
  • Living in a household where the primary language spoken at home is not a language in which we can administer the Wechsler Preschool and Primary School Intelligence Scale
  • Planned postoperative sedation with any agent except opioids (e.g. benzodiazepines, dexmedetomidine, ketamine, barbiturates, propofol, clonidine, chloral hydrate, and other non-opioid sedatives). For example if such sedation is planned for post-operative ventilation

Gender

All

Ages

2 Years and younger

Accepts Healthy Volunteers

No

Study Locations and Contact Information (30)

Study Location Distance Name Phone Email
Boston Childrens Hospital - Boston, Massachusetts 2.6 miles Mary Ellen McCann None Mary.McCann@childrens.harvard.edu
Boston Childrens Hospital - Boston, Massachusetts 2.6 miles Mary Ellen McCann None Mary.McCann@childrens.harvard.edu
Boston Childrens Hospital - Boston, Massachusetts 2.6 miles Mary Ellen McCann None Mary.McCann@childrens.harvard.edu
Boston Childrens Hospital - Boston, Massachusetts 2.6 miles Mary Ellen McCann None Mary.McCann@childrens.harvard.edu
Boston Childrens Hospital - Boston, Massachusetts 2.6 miles Mary Ellen McCann None Mary.McCann@childrens.harvard.edu
The Childrens Hospital of Philadelphia - Philadelphia, Pennsylvania 270.8 miles Francis X McGowan None McGowanF@email.chop.edu
The Childrens Hospital of Philadelphia - Philadelphia, Pennsylvania 270.8 miles Francis X McGowan None McGowanF@email.chop.edu
The Childrens Hospital of Philadelphia - Philadelphia, Pennsylvania 270.8 miles Francis X McGowan None McGowanF@email.chop.edu
The Childrens Hospital of Philadelphia - Philadelphia, Pennsylvania 270.8 miles Francis X McGowan None McGowanF@email.chop.edu
The Childrens Hospital of Philadelphia - Philadelphia, Pennsylvania 270.8 miles Francis X McGowan None McGowanF@email.chop.edu
Cincinnati Childrens Hospital Medical Center - Cincinnati, Ohio 735.6 miles Andreas W Loepke MD 513-636-4408 Andreas.Loepke@cchmc.org
Cincinnati Childrens Hospital Medical Center - Cincinnati, Ohio 735.6 miles Andreas W Loepke MD 513-636-4408 Andreas.Loepke@cchmc.org
Cincinnati Childrens Hospital Medical Center - Cincinnati, Ohio 735.6 miles Andreas W Loepke MD 513-636-4408 Andreas.Loepke@cchmc.org
Cincinnati Childrens Hospital Medical Center - Cincinnati, Ohio 735.6 miles Andreas W Loepke MD 513-636-4408 Andreas.Loepke@cchmc.org
Cincinnati Childrens Hospital Medical Center - Cincinnati, Ohio 735.6 miles Andreas W Loepke MD 513-636-4408 Andreas.Loepke@cchmc.org
The University of Texas Southwestern Medical Center - Dallas, Texas 1,543.9 miles Peter Szmuk MD 214-456-8559 Peter.Szmuk@UTSouthwestern.edu
The University of Texas Southwestern Medical Center - Dallas, Texas 1,543.9 miles Peter Szmuk MD 214-456-8559 Peter.Szmuk@UTSouthwestern.edu
The University of Texas Southwestern Medical Center - Dallas, Texas 1,543.9 miles Peter Szmuk MD 214-456-8559 Peter.Szmuk@UTSouthwestern.edu
The University of Texas Southwestern Medical Center - Dallas, Texas 1,543.9 miles Peter Szmuk MD 214-456-8559 Peter.Szmuk@UTSouthwestern.edu
The University of Texas Southwestern Medical Center - Dallas, Texas 1,543.9 miles Peter Szmuk MD 214-456-8559 Peter.Szmuk@UTSouthwestern.edu
Texas Childrens Hospital - Houston, Texas 1,609.9 miles Dean B Andropoulos MD 832-826-5831 dra@bcm.edu
Texas Childrens Hospital - Houston, Texas 1,609.9 miles Dean B Andropoulos MD 832-826-5831 dra@bcm.edu
Texas Childrens Hospital - Houston, Texas 1,609.9 miles Dean B Andropoulos MD 832-826-5831 dra@bcm.edu
Texas Childrens Hospital - Houston, Texas 1,609.9 miles Dean B Andropoulos MD 832-826-5831 dra@bcm.edu
Texas Childrens Hospital - Houston, Texas 1,609.9 miles Dean B Andropoulos MD 832-826-5831 dra@bcm.edu
Oregon Health and Science University - Portland, Oregon 2,538.3 miles Ansgar M Brambrink MD 503-494-8311 brambrin@ohsu.edu
Oregon Health and Science University - Portland, Oregon 2,538.3 miles Ansgar M Brambrink MD 503-494-8311 brambrin@ohsu.edu
Oregon Health and Science University - Portland, Oregon 2,538.3 miles Ansgar M Brambrink MD 503-494-8311 brambrin@ohsu.edu
Oregon Health and Science University - Portland, Oregon 2,538.3 miles Ansgar M Brambrink MD 503-494-8311 brambrin@ohsu.edu
Oregon Health and Science University - Portland, Oregon 2,538.3 miles Ansgar M Brambrink MD 503-494-8311 brambrin@ohsu.edu

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