Roberts Ian, Belli Antonio, Brenner Amy, Chaudhri Rizwana, Fawole Bukola, Harris Tim, Jooma Rashid, Mahmood Abda, Shokunbi Temitayo, Shakur Haleema
Clinical Trials Unit, LSHTM, London, WC1E 7HT, UK.
The National Institute for Health Research Surgical Reconstruction and Microbiology Research Centre, Queen Elizabeth Hospital, Birmingham, UK.
Wellcome Open Res. 2018 Sep 26;3:86. doi: 10.12688/wellcomeopenres.14700.2. eCollection 2018.
Worldwide, traumatic brain injury (TBI) kills or hospitalises over 10 million people each year. Early intracranial bleeding is common after TBI, increasing the risk of death and disability. Tranexamic acid reduces blood loss in surgery and death due to bleeding in trauma patients with extra-cranial injury. Early administration of tranexamic acid in TBI patients might limit intracranial bleeding, reducing death and disability. The CRASH-3 trial aims to provide evidence on the effect of tranexamic acid on death and disability in TBI patients. We will randomly allocate about 13,000 TBI patients (approximately 10,000 within 3 hours of injury) to an intravenous infusion of tranexamic acid or matching placebo in addition to usual care. This paper presents a protocol update (version 2.1) and statistical analysis plan for the CRASH-3 trial. The primary outcome is head injury death in hospital within 28 days of injury for patients treated within 3 hours of injury (deaths in patients treated after 3 hours will also be reported). Because there are reasons to expect that tranexamic acid will be most effective in patients treated immediately after injury and less effective with increasing delay, the effect in patients treated within one hour of injury is of particular interest. Secondary outcomes are all-cause and cause-specific mortality, vascular occlusive events, disability based on the Disability Rating Scale and measures suggested by patient representatives, seizures, neurosurgical intervention, neurosurgical blood loss, days in intensive care and adverse events. Sub-group analyses will examine the effect of tranexamic acid on head injury death stratified by time to treatment, severity of TBI and baseline risk. The CRASH-3 trial will provide reliable evidence of the effectiveness and safety of tranexamic acid in patients with acute TBI. International Standard Randomised Controlled Trials registry ( ISRCTN15088122) 19/07/2011, and ClinicalTrials.gov ( NCT01402882) 25/07/2011.
在全球范围内，创伤性脑损伤（TBI）每年导致超过1000万人死亡或住院。创伤性脑损伤后早期颅内出血很常见，会增加死亡和残疾风险。氨甲环酸可减少手术中的失血以及因颅外损伤的创伤患者出血导致的死亡。在创伤性脑损伤患者中早期使用氨甲环酸可能会限制颅内出血，降低死亡和残疾率。CRASH - 3试验旨在提供关于氨甲环酸对创伤性脑损伤患者死亡和残疾影响的证据。除常规治疗外，我们将把约13000名创伤性脑损伤患者（约10000名在受伤后3小时内）随机分配接受氨甲环酸静脉输注或匹配的安慰剂治疗。本文介绍了CRASH - 3试验的方案更新（版本2.1）和统计分析计划。主要结局是受伤后3小时内接受治疗的患者在受伤后28天内的颅脑损伤死亡（受伤后3小时后接受治疗患者的死亡情况也将报告）。由于有理由预期氨甲环酸在受伤后立即接受治疗的患者中效果最佳，且随着延迟时间增加效果会降低，因此受伤后1小时内接受治疗患者的效果尤为令人关注。次要结局包括全因死亡率和特定原因死亡率、血管闭塞事件、基于残疾评定量表以及患者代表建议的测量方法得出的残疾情况、癫痫发作、神经外科干预、神经外科失血量、重症监护天数和不良事件。亚组分析将按治疗时间、创伤性脑损伤严重程度和基线风险分层，研究氨甲环酸对颅脑损伤死亡的影响。CRASH - 3试验将为氨甲环酸在急性创伤性脑损伤患者中的有效性和安全性提供可靠证据。国际标准随机对照试验注册库（ISRCTN15088122）2011年7月19日，以及美国国立医学图书馆临床试验注册库（ClinicalTrials.gov，NCT01402882）2011年7月25日。
