External Lumbar Drainage to Abort Severe Traumatic IntraCranial Hypertension: A Phase 1 Randomized, Allocation-concealed, Open-label, Safety and Feasibility Clinical Trial
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 30
- 试验地点
- 11
- 主要终点
- Safety of ELD in selected Severe TBI patients
研究概览
简要总结
The goal of this phase 1 randomized controlled safety and feasibility clinical trial are to determine the safety of external lumbar drainage (ELD) in select patients with severe Traumatic Brain Injury (TBI). The main questions it aims to answer are (i) if ELD is feasible and (ii) safe to perform in severe TBI patients who have radiological evidence of patent basal cisterns and midline shift <5mm without increasing the risk of neurological worsening or cerebral herniation.
All participants will receive routine usual care. The study group will additionally have ELD for cerebrospinal fluid (CSF) drainage. A comparison will be made between the usual treatment plus ELD (interventional) groups, and the usual treatment (control) groups on incidence rate of neurological worsening or cerebral herniation events, and whether total hours with raised intracranial pressure (ICP) are different.
详细描述
This is a randomized controlled trial to determine the safety and feasibility of external lumbar drainage (ELD) of cerebrospinal fluid (CSF) as an adjunct to existing treatments to lower brain pressure, in select patients suffering severe traumatic brain injury (TBI). This trial is funded by the Department of Defense, Uniformed Services University of Health Sciences, Center for Neuroscience and Regenerative Medicine (CNRM).
Following a severe TBI, the brain swells and the pressure in the cranium rises causing further brain injury, The goal of treatment of such patients is to use treatments that lower brain swelling or pressure - directly by removing blood clots or indirectly by trying to lower the volume of contents in the cranium, viz. CSF or blood. Routinely a drain is placed in the skull to drain CSF out to provide space for brain swelling, thus keeping intracranial pressure (ICP) low. In some instances, all treatments available are unable to control swelling and the skull may need to be removed from one side, and in spite of this patients may die or suffer severe neurological injury and remain disabled.
Several non-randomized studies have shown that ELD is very effective in lowering intracranial pressure (ICP) in an immediate and lasting manner. While historical concerns remain that the brain may shift downwards causing herniation, this is not supported by recent studies. However, due to the historic nature of such teachings, some physicians may not use this potentially effective treatment in treating severe TBI patients with high ICP.
Therefore, in this trial we will determine the safety ELD in treating severe TBI patients, in a randomized controlled manner, whereby two-thirds of the patients will be randomized to routine usual treatments and either early or late ELD, and a third to only routine usual treatments. The patient randomized to ELD will receive this in addition to all other usual treatments, and no available treatment will be withheld
The secondary objectives are to determine if routine quantitative pupillometry can be used for safety determination and monitoring of ELD by evaluating:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
Unaware of randomisation arm
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •18-65 years age
- •Glasgow Coma Scale (GCS) 3-8
- •Pupils symmetric and bilaterally reactive
- •Midline shift ≤5mm at the level of foramen of Monro on admission or post-operative brain CT
- •Patent (complete or partial) quadrigeminal cisterns on admission or post-operative brain CT
- •First randomization and intervention may be commenced within 24 hours of injury
- •ELD safety score ≥5
排除标准
- •Cisterns on CT completely effaced
- •Midline shift on CT >5mm
- •GCS 3 with dilated and fixed pupils
- •Uncal or tonsillar herniation on admission or post-operative brain CT
- •Temporal lobe contusions with effaced ipsilateral cisterns
- •Penetrating TBI
- •Primary hemicraniectomy
- •Patients previously lacking capacity to consent or refuse treatment, or with advanced directives to forego aggressive care
- •Pre-existing conditions affecting functional status or life expectancy to less than 1 year
- •Contra-indications for ELD placement: coagulopathy, use of anticoagulants or anti-thrombotics, thrombocytopenia <50,000, or severe spinal deformity.
- •posterior fossa hemorrhage
研究组 & 干预措施
2nd stage - treatment
External lumbar drainage @20mmHg if / when intracranial pressure >20mmHg and tier 1 therapies cannot achieve ICP<20mmHg
干预措施: External Lumbar drainage (Procedure)
Usual treatment
Usual treatment as per SIBICC algorithm
1st stage - prophylactic
External lumbar drainage @15mmHg if intracranial pressure is not raised on admission
干预措施: External Lumbar drainage (Procedure)
结局指标
主要结局
Safety of ELD in selected Severe TBI patients
时间窗: 10 days
Rate of occurrence of herniation events or death in 3 arms
Feasibility of ELD in selected Severe TBI patients
时间窗: 10 days
Proportion of patients able to undergo treatment as per randomised arm
次要结局
- Reduction in ICP burden using ELD in selected severe TBI patients(10 days)
- Utility of automated pupillometry to predict safety of ELD(10 days)
研究者
Halinder Mangat
Director of Research
Brain Trauma Foundation