Brain Oxygen Optimization in Severe Traumatic Brain Injury - Phase 3 (BOOST-3)

创伤性脑损伤是人类死亡和致残的主要原因。在350万美国人中， 每年大约有27,000人经历长期创伤性昏迷，这是最严重的脑损伤形式。 这些患者中只有不到20%的人康复良好，大多数人留下了终生残疾。加护病房 重型颅脑损伤的治疗重点是监测颅内压(ICP)，但最近的数据 进行的随机临床试验表明，这种方法过于简单化。另一种方法是 监测脑组织中的氧分压(PbtO2)，并应用干预措施防止脑组织 低氧和改善神经预后。临床研究表明，脑组织缺氧是常见的， 低PbtO2与不良结局之间有很强的联系，及时的干预可以 逆转脑组织缺氧。首个重型颅脑损伤患者PbtO2监测的随机对照试验 “重型颅脑损伤(Boost)第二阶段的脑氧优化”招募了122名受试者，并证明了 通过PbtO2监测通知的治疗方案，平均低氧负荷降低了74%(p&lt； 0.0001)，并且没有重大的安全问题。有改善功能结果的趋势， 支持预先确定的非徒劳假说。我们提议进行Boost-3试验，以确定 有证据表明，与治疗相比，基于PbtO2监测的治疗方案具有临床疗效 仅根据国际比较方案监测。Boost-3将招募需要放置颅内压的重型颅脑损伤患者 在向参与计划的医院演示后6小时内提供监护仪。患者将随机接受一种治疗 基于单独监测ICP或联合监测ICP和PbtO2的议定书。《格拉斯哥报》 伤后6个月评定的结果量表(GOS-E)将是主要结果。其他 次要结果包括6个月后的功能、认知和行为评估、安全性、生存期和 放电，缩短听从指令的时间，并减少总的脑缺氧暴露。

Traumatic brain injury (TBI) is a major cause of death and disability. Of the 3.5 million Americans who sustain a TBI every year, approximately 27,000 experience prolonged traumatic coma, the most severe form of TBI. Less than 20% of these patients make a good recovery, and most are left with life-long disabilities. ICU management of severe TBI focuses on monitoring intracranial pressure (ICP), but data from recently conducted randomized clinical trials indicate that this approach is overly simplistic. Another approach is to monitor the partial pressure of oxygen in brain tissue (PbtO2) and apply interventions to prevent brain tissue hypoxia and improve neurologic outcome. Clinical studies demonstrate that brain tissue hypoxia is common, that there is a strong relationship between low PbtO2 and poor outcome, and that timely interventions can reverse brain tissue hypoxia. The first randomized controlled trial of PbtO2 monitoring in severe TBI, titled “Brain Oxygen Optimization in Severe TBI (BOOST) Phase 2,” enrolled 122 subjects and demonstrated that the mean hypoxia burden was reduced by 74% by the treatment protocol informed by PbtO2 monitoring (p < 0.0001), and there were no significant safety issues. There was a trend towards improved functional outcome, supporting the pre-determined non-futility hypothesis. We are proposing the BOOST-3 trial to determine if there is evidence of clinical efficacy of a treatment protocol based on PbtO2 monitoring compared to treatment based on ICP monitoring alone. BOOST-3 will enroll patients with severe TBI requiring placement of ICP monitors within 6 hours of presentation to a participating hospital. Patients will be randomized to a treatment protocol based on ICP monitoring alone or the combination of ICP and PbtO2 monitoring. The Glasgow Outcome Scale-Extended (GOS-E) measured at 6 months post injury will be the primary outcome. Other secondary outcomes include functional, cognitive and behavioral assessments at 6 months, safety, survival to discharge, shortened time to follow commands, and reduction of total brain hypoxia exposure.