두 가지 다른 마취 후 장기 결과를 비교하는 연구 (TREX)
유아의 표준 용량 Sevoflurane 대 저용량 Sevoflurane/Dexmedetomidine/Remifentanil 마취 후 신경 발달 결과 - TREX 시험
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.
연구 개요
상태
상태
정황
정황
개입 / 치료
개입 / 치료
연구 유형
연구 유형
등록 (실제)
등록
단계
단계
- 3단계
연락처 및 위치
연구 장소
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Massachusetts
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Boston, Massachusetts, 미국, 02115
- Boston Children's Hospital
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Ohio
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Cleveland, Ohio, 미국, 44195
- Cleveland Clinic
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Pennsylvania
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Philadelphia, Pennsylvania, 미국, 19104
- The Children's Hospital of Philadelphia
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Texas
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Dallas, Texas, 미국, 75390
- The University of Texas Southwestern Medical Center
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Houston, Texas, 미국, 77030
- Texas Children's Hospital
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Madrid, 스페인
- La Paz University Hospital
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Alessandria, 이탈리아
- Presidio Ospedale Infantile C.Arrigo Azienda Ospedaliera
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Bologna, 이탈리아
- Azienda ospedaliero-universitaria di Bologna
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Florence, 이탈리아
- Azienda Ospedaliero-Universitaria Meyer
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Genova, 이탈리아
- Istituto Giannina Gaslini
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Milan, 이탈리아
- Vittore Buzzi Children's Hospital
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Milan, 이탈리아
- Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico - Clinica Mangiagalli
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Pisa, 이탈리아
- Azienda Ospedaliero Universitaria Pisana
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Roma, 이탈리아
- Ospedale Bambino Gesù
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New South Wales
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Randwick, New South Wales, 호주, 2031
- Sydney Children's Hospital
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Westmead, New South Wales, 호주, 2145
- Children's Hospital at Westmead
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Queensland
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Brisbane, Queensland, 호주, 4101
- Queensland Children's Hospital
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South Australia
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Adelaide, South Australia, 호주, 5006
- Women's and Children's Hospital
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Bedford Park, South Australia, 호주, 5042
- Flinders Medical Centre
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Victoria
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Parkville, Victoria, 호주, 3052
- Royal Children's Hospital
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Western Australia
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Perth, Western Australia, 호주, 6008
- Perth Children's Hospital
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참여기준
자격 기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
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
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 하나의
팔의 수
무기와 개입
참가자 그룹 / 팔참가자 그룹 / 팔 |
개입 / 치료개입 / 치료 |
|---|---|
|
실험적: 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.
다른 이름들:
Experimental arm: loading dose: 1 mcg/kg, infusion starting at 0.1 mcg/kg/min or greater.
다른 이름들:
Experimental arm: loading dose:1mcg/kg, infusion: 1 mcg/kg/hr.
다른 이름들:
|
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활성 비교기: 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.
다른 이름들:
|
연구는 무엇을 측정합니까?
주요 결과 측정
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Full Scale IQ
기간: 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
|
2차 결과 측정
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
incidence of intra-operative hypotension
기간: 150 minutes- duration of surgery (baseline)
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Blood pressure measurements will be recorded during surgery |
150 minutes- duration of surgery (baseline)
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incidence of intra-operative bradycardia
기간: 150 minutes- duration of surgery (baseline)
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Heart rate will be recorded during surgery |
150 minutes- duration of surgery (baseline)
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Post-operative pain
기간: 60 minutes- after surgery
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Pain scores will be recorded after surgery |
60 minutes- after surgery
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Time to recovery
기간: 60 minutes- after surgery
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Time of removal of airway, eye-opening and discharge from PACU will be recorded. |
60 minutes- after surgery
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Language outcomes
기간: 3 years of age
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Clinical Evaluation of Language Fundamentals- Preschool, Version 2 (CELF-P2) |
3 years of age
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Attention/Executive Function/impulse control
기간: 3 years of age
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A Developmental NEuroPSYchological Assessment- Second Edition (NEPSY-2): Statue Subtest |
3 years of age
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Memory
기간: 3 years of age
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A Developmental NEuroPSYchological Assessment- Second Edition (NEPSY-2): Narrative memory |
3 years of age
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Adaptive behaviour
기간: 3 years of age
|
Adaptive Behavior Assessment System - Third Edition (ABAS-III) |
3 years of age
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Clinical Behavior
기간: 3 years of age
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Child Behavior Checklist (CBCL) |
3 years of age
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Executive Function
기간: 3 years of age
|
Behavior Rating of Executive Function- Preschool (BRIEF-P) |
3 years of age
|
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Social Skills
기간: 3 years of age
|
Social Skills Improvement System (SSIS) |
3 years of age
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공동 작업자 및 조사자
협력자
협력자
수사관
수사관
- 연구 의자: Andrew J Davidson, MD, Royal Children's Hospital
간행물 및 유용한 링크
일반 간행물
- 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.
연구 기록 날짜
연구 주요 날짜
연구 시작 (실제)
연구 시작
기본 완료 (추정된)
기본 완료
연구 완료 (추정된)
연구 완료
연구 등록 날짜
최초 제출
최초 제출
QC 기준을 충족하는 최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
처음 게시됨
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
마지막 업데이트 게시됨
QC 기준을 충족하는 마지막 업데이트 제출
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
기타 연구 ID 번호
- TREX TRIAL
- 2024-512385-34-00 (씨티스)
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
IPD 계획 설명
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.
IPD 공유 기간
6 months after publication of primary outcome
IPD 공유 액세스 기준
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.
IPD 공유 지원 정보 유형
- 연구_프로토콜
- 수액
- ICF
- ANALYTIC_CODE
- CSR
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
미국 FDA 규제 기기 제품 연구
미국에서 제조되어 미국에서 수출되는 제품
이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .