Brain Injury and Ketamine: a Prospective, Randomized Controlled Double Blind Clinical Trial to Study the Effects of Ketamine on Sedative Sparing and Intracranial Pressure in Traumatic Brain Injury Patients.
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 100
- 试验地点
- 8
- 主要终点
- Change in therapeutic intensity of intracranial pressure (ICP) reducing measures, assessed by the TIL score (Therapy Intensity Level)
研究概览
简要总结
Although, in the past years, an increasing use of ketamine in Traumatic Brain injury (TBI) has been reported as an adjunct to other sedatives, there is no evidence from randomized clinical trial to support this practice.
The BIKe (Brain Injury and Ketamine) study is a double-blind placebo controlled randomized multicenter clinical trial to examine the safety and feasibility of using ketamine as an adjunct to a standard sedative strategy in TBI patients.
详细描述
In this study the effects of ketamine as an adjunct to an standard sedation regime in adult TBI patients will be investigated on the therapy intensity level and intracranial pressure. All patients will receive propofol for sedation to control ICP, to a maximum dose of 4 mg/kg/h. If the ICP is not controlled at the maximum dose of propofol, midazolam will be added, to a maximum dose of 0.3 mg/kg/h, as part of the current standard of care in the Participating Sites. All patients will receive remifentanil, fentanyl or sufentanil infusions for pain relief. The study medication (ketamine or placebo) will be started after randomization.
As part of the current standard of care in the Participating Sites, the decision for decompressive craniectomy and/or barbiturate coma will be taken after multidisciplinary consultation between the treating intensivist and neurosurgeon.
The decision to stop or reduce sedation, lies with the treating physician, based on the level of ICP control, the absence of clinical or radiological signs of deterioration of the neurologic state. In the case of barbiturate coma, the study drug will be discontinued. During and following decompressive craniectomy, the sedative regime (propofol/midazolam/study drug/ opioids) will be continued. In case of suspected or threatening Propofol-Related Infusion syndrome, propofol will be stopped and switched to midazolam. In case of hypertriglyceridemia >200 mg/dL, propofol will be reduced and if necessary, midazolam will be associated to allow control of sedation. During surgical procedures related to the traumatic brain injury or not, the study drug will not be discontinued. The use of open label administration of ketamine is not allowed during the course of the trial, i.e until hospital discharge.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- Double (Participant, Care Provider)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Traumatic brain injury patients
- •Age >= 18 years
- •Admitted to the ICU
- •Within 72 hours after admission to the initial hospital:
- •ICP monitoring in place (parenchymal probe, ventricular catheter, or both)
- •Requiring sedation
排除标准
- •Known pregnancy and/or lactation
- •Imminent or actual brain death upon inclusion
- •Allergy or intolerance to the study medication
- •Pre-existing neurocognitive disorders, pre-existing congenital or non-congenital brain dysfunction.
- •Inability to obtain informed consent
- •Inclusion in an interventional randomised controlled trial of which the PI indicates that co-inclusion specifically in the BIKe study is prohibited.
- •Therapy restriction code upon inclusion.
- •Porphyria
研究组 & 干预措施
Ketamine
Racemic ketamine® will be administered by continuous infusion in a prefilled 50 ml syringe at a concentration of 50 mg/ml, undiluted. The ketamine dose is 1 mg/kg/h, to a maximum dose of 120 mg/hour, which corresponds to an infusion rate of 0.02 ml/kg/h to a maximum rate of 2.4 ml/h. Study patients weighing over 120 kg will not exceed the maximum dose of 120mg/kg of ketamine.
The study medication will be started within 6 hours after randomization. The IMP, ketamine, will be provided directly to each Participating Site by the official supplier of ketamine for Belgium (Pfizer).
干预措施: Ketamine (Drug)
Placebo
The placebo (NaCl 0.9%) will be provided in the same type syringes and administered at the same infusion rate as the IMP (0.02 ml/kg/h to a maximum rate of 2.4 ml/h).
干预措施: Placebo (Drug)
结局指标
主要结局
Change in therapeutic intensity of intracranial pressure (ICP) reducing measures, assessed by the TIL score (Therapy Intensity Level)
时间窗: From date of randomization (and start study drug) until study drug discontinuation or date of death from any cause, whichever came first, assessed up to 6 months.
The primary efficacy endpoint will be the reduction in daily Therapy Intensity Level (TIL) score, based on the highest score in each item per day until study drug discontinuation (calculated every day on the available data at 7:00 AM). Scales for TIL score range from 0 (minimum) to 38 (maximum). Higher scores are related to worse outcome.
次要结局
- Richmond Agitation-Sedation scale (RASS)(From date of randomization until study drug discontinuation or date of death from any cause, whichever came first, assessed up to 6 months.)
- eGOS(6 months after the onset of TBI)
- In-hospital mortality(From date of randomization until hospital discharge, assessed up to 6 months.)
- Barbiturate coma incidence(From date of randomization until study drug discontinuation or date of death from any cause, whichever came first, assessed up to 6 months.)
- Intracranial pressure (ICP)(From date of randomization until study drug discontinuation or or date of death from any cause, whichever came first, assessed up to 6 months.)
- Duration of sedation(defined as the start of the first infusion of either propofol, midazolam and/or dexmedetomidine to the cessation of the last uninterrupted infusion of either propofol, midazolam, opioids and/or dexmedetomidine, assessed up to 6 months.)
- Midazolam(From date of randomization until study drug discontinuation or date of death from any cause, whichever came first, assessed up to 6 months.)
- Mechanical ventilation(From date of randomization until study drug discontinuation or date of death from any cause, whichever came first, assessed up to 6 months.)
- ICU length of stay(From ICU admission until ICU discharge (end of stay is defined as application for discharge in the hospital computer system, or death), assessed up to 6 months.)
- Hospital length of stay(From admission to hospital until end of stay in hospital (dead or alive), assessed up to 6 months.)
- Delirium(From date of randomization until study drug discontinuation or date of death from any cause, whichever came first, assessed up to 6 months.)
- Barbiturate coma duration(From date of randomization until study drug discontinuation or date of death from any cause, whichever came first, assessed up to 6 months.)
- Propofol(From date of randomization until study drug discontinuation or date of death from any cause, whichever came first, assessed at ICU discharge, assessed up to 6 months.)
- ICU mortality(From date of randomization until ICU discharge, assessed up to 6 months.)
- Decompressive craniectomy(From date of randomization until study drug discontinuation or date of death from any cause, whichever came first, assessed up to 6 months, assessed up to 6 months.)
- Propofol Infusion Syndrome (PRIS)(From date of randomization until study drug discontinuation or date of death from any cause, whichever came first, assessed up to 6 months.)
研究者
Geert Meyfroidt, MD, PhD
Associate Professor of Medicine
KU Leuven