Age Related Thresholds For Management Of Severe Head Injury In Paediatrics: ARTSHIP
试验速览
- 阶段
- 不适用
- 状态
- Enrolling By Invitation
- 入组人数
- 450
- 试验地点
- 1
- 主要终点
- Glasgow Outcome Score Extended for Pediatrics
研究概览
简要总结
Traumatic brain injury in children can cause serious and long-lasting neuro-disability. However, there is still limited evidence about the best ways to treat children with severe brain injury in intensive care.
One important part of treatment is managing pressure inside the skull and ensuring that the brain receives enough blood and oxygen. Current international guidelines provide treatment targets, but these recommendations are based on relatively limited research in children. This is particularly challenging because children range from infants to teenagers, and the developing brain changes considerably with age. A single treatment target may therefore not be appropriate for every child. Carrying out large clinical trials in critically ill children is difficult for both practical and ethical reasons. An alternative approach is to combine information that is already being collected during routine intensive care and use these large datasets to better understand which treatments may be most helpful.
Our previous multicentre study, STARSHIP, collected detailed information from 135 children with traumatic brain injury. The study combined clinical information with continuous measurements of brain-related physiology. One of these measurements, called the pressure reactivity index (PRx), provides information about how well the brain is able to regulate its own blood supply. We found that PRx was associated with patient outcomes, regardless of the initial severity of the injury, and that treatment practices varying between hospitals. We also found that changes in PRx over time may provide useful information about recovery and outcome.
The STARSHIP study has created a valuable research database that allows us to explore how measurements such as pressure inside the skull, blood flow to the brain, and the brain's ability to regulate its blood supply relate to recovery. However, there were not enough children within each age group to determine whether different treatment targets should be used for infants, younger children, and teenagers.
Several hospitals in the UK and internationally have collected similar detailed information. Through this project, these centres will work together to combine their existing datasets, creating a much larger group of approximately 350-500 children with traumatic brain injury.
By analysing this larger dataset, we hope to identify treatment targets that are more appropriate for children of different ages. In particular, we will study pressure inside the skull, blood pressure supplying the brain, and the brain's ability to regulate its own blood flow.
Ultimately, this research could help doctors move away from a "one-size-fits-all" approach and towards more personalised treatment for children with severe traumatic brain injury. By identifying age-appropriate and patient-specific treatment targets, we hope to improve brain protection and, ultimately, outcomes for injured children.
详细描述
- Background Neuro-morbidity associated with TBI in children is high and there is limited available evidence for strategies to improve outcomes1. The last international guideline for management of severe TBI in children were mainly based on level III evidence due to lack of robust evidence for age related thresholds for treatment targets in paediatric intensive care (PICU) like intracranial pressure (ICP) and cerebral perfusion pressure (CPP), or availability of methods to individualise these targets, like indices of cerebral autoregulation (CA)2. As the paediatric age range encompasses a developmental trajectory, combined with the disease heterogeneity, single treatment thresholds are insufficient for the best outcomes in paediatric TBI (pTBI). Given the ethical challenges and difficulties with doing research in children and poor yield from randomized controlled trials, there is increasing recognition of using big data to answer research questions.
We have recently completed the multicentre prospective research database study, STARSHIP including 135 pTBI patients with promising results confirming PRx association with outcome irrespective of the initial disease severity, ICP and CPP, and centre specific differences in management3. We have also identified dynamic temporal trends of PRx and its thresholds for outcome. In this process, we have also created a rich research database with time-synchronized physiological information with clinical and outcome data which has been used to further explore the thresholds for ICP and CPP related to outcome. However, the small number of patients in each age category does not allow identification of age-appropriate thresholds. STARSHIP has ethics approval as a research database which allows for the database to be combined with other databases. There are similar datasets that exists in individual centers, (for eg, Cambridge pTBI dataset prior to STARSHIP, Birmingham Children's Hospital in the UK; Phoenix Children's Hospital in the USA; Uppsala, Leuven and Rotterdam in Europe, to name a few). Given the small numbers of pTBI, all these centers have come together to collaborate to make a meaningful impact by combining datasets.
Through this project, we propose to combine similar existing datasets from other UK and international centres to create a larger cohort (350- 500 patients) of pTBI patients. This will facilitate statistically meaningful analysis of age-stratified thresholds, namely ICP, CPP and PRx using the same analytical methods we have used for STARSHIP3,4. The larger dataset analysis may help stratify CA guided treatment targets for neuroprotection across the paediatric age range. 2. Rationale & Theoretical Framework We will use the combined dataset to identify age-appropriate treatment thresholds for neuroprotection, i.e., ICP and CPP in severe pTBI for improved outcomes as well test if the PRx thresholds are different in different age ranges. The results of this study would be crucial to fill some of the gaps in current evidence base for managing children with severe TBI. This will help with planning future prospective interventional studies to evaluate if the age-appropriate and CA guided treatment thresholds can improve outcomes in children with TBI.
The study will help stratification of age-based thresholds for treatment targets used in managing severe pTBI with the hypothesis that there would be different thresholds for ICP and CPP depending on the patients age and autoregulatory status. The results should inform the international evidence-based guidelines as well as future research by creating foundation for phase II/III studies to test the hypothesis in prospective clinical studies. 3. Research Question/Aims and Objectives:
To identify age-stratified thresholds of treatment targets for neuroprotection, namely intracranial pressure (ICP), cerebral perfusion pressure (CPP) and cerebral autoregulation (PRx) in children with traumatic brain injury. 4. Study Design/ Methods:
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Other
入排标准
- 年龄范围
- 1 Month 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Datasets will be eligible if they contain at least 15 children with TBI and include:
- •patients younger than 18 years at the time of injury;
- •invasive advanced neuromonitoring including ICP and ABP;
- •high-resolution physiologic waveform data, preferably sampled at 100 Hz or greater;
- •at least 6 hours of analyzable physiologic recording per patient;
- •sufficient demographic and clinical information to characterize TBI severity; and
- •functional outcome assessment approximately 6 months after injury. Twelve-month outcome information will also be included where available.
排除标准
- 未提供
研究组 & 干预措施
STARSHIP
Research Database
Leuven
Leuven pTBI patients cohort
Phoenix
Phoenix pTBI patients cohort
Rotterdam
Rotterdam pTBI patients cohort
Cambridge
Cambridge pTBI patients cohort
BIrmingham
Birmingham pTBI patients cohort
Uppasala
Uppasala pTBI patients cohort
结局指标
主要结局
Glasgow Outcome Score Extended for Pediatrics
时间窗: 6 months
Ordinal global neurological outcome scoring system
次要结局
- Glasgow Outcome Score Extended for Pediatrics(12 months)
研究者
Shruti Agrawal
PICU Consultant
Cambridge University Hospitals NHS Foundation Trust