Studie k porovnání dlouhodobých výsledků po dvou různých anestetikech (TREX)
Neurovývojový výsledek po standardní dávce sevofluranu versus nízké dávky sevofluranu/dexmedetomidinu/remifentanilové anestezie u malých dětí – studie TREX
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.
Přehled studie
Postavení
Podmínky
Intervence / Léčba
Typ studie
Zápis (Aktuální)
Fáze
- Fáze 3
Kontakty a umístění
Studijní místa
-
-
New South Wales
-
Randwick, New South Wales, Austrálie, 2031
- Sydney Children's Hospital
-
Westmead, New South Wales, Austrálie, 2145
- Children's Hospital at Westmead
-
-
Queensland
-
Brisbane, Queensland, Austrálie, 4101
- Queensland Children's Hospital
-
-
South Australia
-
Adelaide, South Australia, Austrálie, 5006
- Women's and Children's Hospital
-
Bedford Park, South Australia, Austrálie, 5042
- Flinders Medical Centre
-
-
Victoria
-
Parkville, Victoria, Austrálie, 3052
- Royal Children's Hospital
-
-
Western Australia
-
Perth, Western Australia, Austrálie, 6008
- Perth Children's Hospital
-
-
-
-
-
Alessandria, Itálie
- Presidio Ospedale Infantile C.Arrigo Azienda Ospedaliera
-
Bologna, Itálie
- Azienda ospedaliero-universitaria di Bologna
-
Florence, Itálie
- Azienda Ospedaliero-Universitaria Meyer
-
Genova, Itálie
- Istituto Giannina Gaslini
-
Milan, Itálie
- Vittore Buzzi Children's Hospital
-
Milan, Itálie
- Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico - Clinica Mangiagalli
-
Pisa, Itálie
- Azienda Ospedaliero Universitaria Pisana
-
Roma, Itálie
- Ospedale Bambino Gesù
-
-
-
-
Massachusetts
-
Boston, Massachusetts, Spojené státy, 02115
- Boston Children's Hospital
-
-
Ohio
-
Cleveland, Ohio, Spojené státy, 44195
- Cleveland Clinic
-
-
Pennsylvania
-
Philadelphia, Pennsylvania, Spojené státy, 19104
- The Children's Hospital of Philadelphia
-
-
Texas
-
Dallas, Texas, Spojené státy, 75390
- The University of Texas Southwestern Medical Center
-
Houston, Texas, Spojené státy, 77030
- Texas Children's Hospital
-
-
-
-
-
Madrid, Španělsko
- La Paz University Hospital
-
-
Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
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
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Randomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Singl
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
|---|---|
|
Experimentální: 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. |
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.
Ostatní jména:
Experimental arm: loading dose: 1 mcg/kg, infusion starting at 0.1 mcg/kg/min or greater.
Ostatní jména:
Experimental arm: loading dose:1mcg/kg, infusion: 1 mcg/kg/hr.
Ostatní jména:
|
|
Aktivní komparátor: Sevoflurane
End tidal concentration of 2.5-3.0% or greater. |
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.
Ostatní jména:
|
Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Full Scale IQ
Časové okno: 3 years of age
|
Global cognitive function as assessed by the full scale IQ score of the Wechsler Preschool and Primary School Intelligence Scale. |
3 years of age
|
Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
incidence of intra-operative hypotension
Časové okno: 150 minutes- duration of surgery (baseline)
|
Blood pressure measurements will be recorded during surgery |
150 minutes- duration of surgery (baseline)
|
|
incidence of intra-operative bradycardia
Časové okno: 150 minutes- duration of surgery (baseline)
|
Heart rate will be recorded during surgery |
150 minutes- duration of surgery (baseline)
|
|
Post-operative pain
Časové okno: 60 minutes- after surgery
|
Pain scores will be recorded after surgery |
60 minutes- after surgery
|
|
Time to recovery
Časové okno: 60 minutes- after surgery
|
Time of removal of airway, eye-opening and discharge from PACU will be recorded. |
60 minutes- after surgery
|
|
Language outcomes
Časové okno: 3 years of age
|
Clinical Evaluation of Language Fundamentals- Preschool, Version 2 (CELF-P2) |
3 years of age
|
|
Attention/Executive Function/impulse control
Časové okno: 3 years of age
|
A Developmental NEuroPSYchological Assessment- Second Edition (NEPSY-2): Statue Subtest |
3 years of age
|
|
Memory
Časové okno: 3 years of age
|
A Developmental NEuroPSYchological Assessment- Second Edition (NEPSY-2): Narrative memory |
3 years of age
|
|
Adaptive behaviour
Časové okno: 3 years of age
|
Adaptive Behavior Assessment System - Third Edition (ABAS-III) |
3 years of age
|
|
Clinical Behavior
Časové okno: 3 years of age
|
Child Behavior Checklist (CBCL) |
3 years of age
|
|
Executive Function
Časové okno: 3 years of age
|
Behavior Rating of Executive Function- Preschool (BRIEF-P) |
3 years of age
|
|
Social Skills
Časové okno: 3 years of age
|
Social Skills Improvement System (SSIS) |
3 years of age
|
Spolupracovníci a vyšetřovatelé
Spolupracovníci
Vyšetřovatelé
- Studijní židle: Andrew J Davidson, MD, Royal Children's Hospital
Publikace a užitečné odkazy
Obecné publikace
- Saynhalath R, Disma N, Taverner FJ, von Ungern-Sternberg BS, Andropoulos D, Ng AS, Shields BB, Izzo F, Lee-Archer P, McCann ME, Montagnini L, Kuppers B, Lenares E, Sheppard S, de Graaff JC, Lee KJ, Wang X, Szmuk P, Davidson AJ, Skowno JJ; TREX (Trial Remifentanil DEXmedetomidine) Consortium. Short-term Outcomes in Infants after General Anesthesia with Low-dose Sevoflurane/Dexmedetomidine/Remifentanil versus Standard-dose Sevoflurane (the TREX Trial). Anesthesiology. 2024 Dec 1;141(6):1075-1085. doi: 10.1097/ALN.0000000000005232.
- Chen DX, Tan ZM, Lin XM. General Anesthesia Exposure in Infancy and Childhood: A 10-year Bibliometric Analysis. J Perianesth Nurs. 2024 Oct;39(5):772-781. doi: 10.1016/j.jopan.2023.12.006. Epub 2024 Mar 21.
- Oltean T, Ostlund S, Rinehart J, Vandenabeele P, Kain ZN, Coeckelenbergh S. Neuronal Cell Death Modalities and Protective Mechanisms Induced By Sevoflurane: A Narrative Review. Anesth Analg. 2026 Oct 1;143(4):807-821. doi: 10.1213/ANE.0000000000008035. Epub 2026 May 6.
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Aktuální)
Primární dokončení (Odhadovaný)
Dokončení studie (Odhadovaný)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Další relevantní podmínky MeSH
- Nemoci nervového systému
- Chemicky indukované poruchy
- Otrava
- Syndromy neurotoxicity
- Organické chemikálie
- Heterocyklické sloučeniny, 1 kruh
- Heterocyklické sloučeniny
- Ethers
- Azoly
- Uhlovodíky
- Kyseliny, acyklické
- Karboxylové kyseliny
- Imidazoly
- Piperidiny
- Uhlovodíky, halogenované
- Uhlovodíky, fluorované
- Propionáty
- MethylEthers
- Remifentanil
- Sevofluran
- Dexmedetomidin
Další identifikační čísla studie
- TREX TRIAL
- 2024-512385-34-00 (Ctis)
Plán pro data jednotlivých účastníků (IPD)
Plánujete sdílet data jednotlivých účastníků (IPD)?
Popis plánu IPD
The de-identified data set collected for this analysis of the TREX trial will be available six months after publication of the primary outcome.
The study protocol, analysis plan and consent forms will also be available. The data may be obtained from the Murdoch Children's Research Institute by emailing andrew.davidson@rch.org.au.
Časový rámec sdílení IPD
6 months after publication of primary outcome
Kritéria přístupu pro sdílení IPD
Prior to releasing any data the following are required: a data access agreement must be signed between relevant parties, the TREX Trial Steering Committee must see and approve the analysis plan describing how the data will be analysed, there must be an agreement around appropriate acknowledgement and any additional costs involved must be covered. Data will only be shared with a recognised research institution which has approved the proposed analysis plan.
Typ podpůrných informací pro sdílení IPD
- PROTOKOL STUDY
- MÍZA
- ICF
- ANALYTIC_CODE
- CSR
Informace o lécích a zařízeních, studijní dokumenty
Studuje lékový produkt regulovaný americkým FDA
Studuje produkt zařízení regulovaný americkým úřadem FDA
produkt vyrobený a vyvážený z USA
Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .