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

NCT ID: NCT03089905

Last Updated: 2025-08-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

450 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-08-10

Study Completion Date

2026-06-30

Brief Summary

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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 anaesthesia expected to last 2 hours or longer.

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.

Detailed Description

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Conditions

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Anesthesia Neurotoxicity Child Development

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Participants will be randomised to receive either low-dose sevoflurane/dexmedetomidine/remifentanil OR standard dose sevoflurane anaesthesia.
Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors
Randomisation 1:1 will be stratified by site and age at exposure (less than 12 months and greater than or equal to 12 months). Randomisation will be in blocks of variable size. The treating anaesthetist will not be blinded to treatment arm. The assessing neuropsychologist and parents will be blinded to treatment arm.

Study Groups

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Sevoflurane/dexmedetomidine/remifentanil

Dexmedetomidine: loading dose of 1mcg/kg over 10 minutes followed by an infusion of at 1 mcg/kg/hr.

Remifentanil: loading dose 1 mcg/kg over 2 minutes followed by an infusion starting at 0.1 mcg/kg/min or greater.

Sevoflurane: end tidal concentration of 0.6 -0.8% or less.

Group Type EXPERIMENTAL

Sevoflurane

Intervention Type DRUG

Experimental arm: end tidal concentration of 0.6 -0.8% or less. Active comparator arm: end tidal concentration of 2.5-3.0% or greater.

Remifentanil

Intervention Type DRUG

Experimental arm: loading dose: 1 mcg/kg, infusion starting at 0.1 mcg/kg/min or greater.

Dexmedetomidine

Intervention Type DRUG

Experimental arm: loading dose:1mcg/kg, infusion: 1 mcg/kg/hr.

Sevoflurane

End tidal concentration of 2.5-3.0% or greater.

Group Type ACTIVE_COMPARATOR

Sevoflurane

Intervention Type DRUG

Experimental arm: end tidal concentration of 0.6 -0.8% or less. Active comparator arm: end tidal concentration of 2.5-3.0% or greater.

Interventions

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Sevoflurane

Experimental arm: end tidal concentration of 0.6 -0.8% or less. Active comparator arm: end tidal concentration of 2.5-3.0% or greater.

Intervention Type DRUG

Remifentanil

Experimental arm: loading dose: 1 mcg/kg, infusion starting at 0.1 mcg/kg/min or greater.

Intervention Type DRUG

Dexmedetomidine

Experimental arm: loading dose:1mcg/kg, infusion: 1 mcg/kg/hr.

Intervention Type DRUG

Other Intervention Names

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Sevorane Ultiva Precedex Dexmedetomidine Ever Pharma

Eligibility Criteria

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Inclusion Criteria

* Younger than 2 years (chronological age)
* Scheduled for anaesthesia that is expected to last at least 2 hours (and/or total operating room time is scheduled to be at least 2.5 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
Maximum Eligible Age

2 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Sydney Children's Hospitals Network

OTHER

Sponsor Role collaborator

Baylor College of Medicine

OTHER

Sponsor Role collaborator

Boston Children's Hospital

OTHER

Sponsor Role collaborator

The Cleveland Clinic

OTHER

Sponsor Role collaborator

University of Texas, Southwestern Medical Center at Dallas

OTHER

Sponsor Role collaborator

Royal Children's Hospital

OTHER

Sponsor Role collaborator

Children's Hospital of Philadelphia

OTHER

Sponsor Role collaborator

Queensland Children's Hospital

OTHER_GOV

Sponsor Role collaborator

Perth Children's Hospital

UNKNOWN

Sponsor Role collaborator

Women and Children's Hospital

UNKNOWN

Sponsor Role collaborator

Istituto Giannina Gaslini

OTHER

Sponsor Role collaborator

Flinders Medical Centre

OTHER_GOV

Sponsor Role collaborator

Murdoch Childrens Research Institute

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Andrew J Davidson, MD

Role: STUDY_CHAIR

Royal Children's Hospital

Locations

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Boston Children's Hospital

Boston, Massachusetts, United States

Site Status

Cleveland Clinic

Cleveland, Ohio, United States

Site Status

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

The University of Texas Southwestern Medical Center

Dallas, Texas, United States

Site Status

Texas Children's Hospital

Houston, Texas, United States

Site Status

Sydney Children's Hospital

Randwick, New South Wales, Australia

Site Status

Children's Hospital at Westmead

Westmead, New South Wales, Australia

Site Status

Queensland Children's Hospital

Brisbane, Queensland, Australia

Site Status

Women's and Children's Hospital

Adelaide, South Australia, Australia

Site Status

Flinders Medical Centre

Bedford Park, South Australia, Australia

Site Status

Royal Children's Hospital

Parkville, Victoria, Australia

Site Status

Perth Children's Hospital

Perth, Western Australia, Australia

Site Status

Presidio Ospedale Infantile C.Arrigo Azienda Ospedaliera

Alessandria, , Italy

Site Status

Azienda ospedaliero-universitaria di Bologna

Bologna, , Italy

Site Status

Azienda Ospedaliero-Universitaria Meyer

Florence, , Italy

Site Status

Istituto Giannina Gaslini

Genova, , Italy

Site Status

Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico - Clinica Mangiagalli

Milan, , Italy

Site Status

Vittore Buzzi Children's Hospital

Milan, , Italy

Site Status

Azienda Ospedaliero Universitaria Pisana

Pisa, , Italy

Site Status

Ospedale Bambino Gesù

Roma, , Italy

Site Status

La Paz University Hospital

Madrid, , Spain

Site Status

Countries

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United States Australia Italy Spain

Provided Documents

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Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2024-512385-34-00

Identifier Type: CTIS

Identifier Source: secondary_id

TREX TRIAL

Identifier Type: -

Identifier Source: org_study_id

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