Importance Traumatic brain injury (TBI) is the leading cause of death and disability due to trauma. Early administration of tranexamic acid may benefit patients with TBI. Objective To determine whether tranexamic acid treatment initiated in the out-of-hospital setting within 2 hours of injury improves neurologic outcome in patients with moderate or severe TBI. Design, Setting, and Participants Multicenter, double-blinded, randomized clinical trial at 20 trauma centers and 39 emergency medical services agencies in the US and Canada from May 2015 to November 2017. Eligible participants (N = 1280) included out-of-hospital patients with TBI aged 15 years or older with Glasgow Coma Scale score of 12 or less and systolic blood pressure of 90 mm Hg or higher. Interventions Three interventions were evaluated, with treatment initiated within 2 hours of TBI: out-of-hospital tranexamic acid (1 g) bolus and in-hospital tranexamic acid (1 g) 8-hour infusion (bolus maintenance group; n = 312), out-of-hospital tranexamic acid (2 g) bolus and in-hospital placebo 8-hour infusion (bolus only group; n = 345), and out-of-hospital placebo bolus and in-hospital placebo 8-hour infusion (placebo group; n = 309). Main Outcomes and Measures The primary outcome was favorable neurologic function at 6 months (Glasgow Outcome Scale-Extended score >4 [moderate disability or good recovery]) in the combined tranexamic acid group vs the placebo group. Asymmetric significance thresholds were set at 0.1 for benefit and 0.025 for harm. There were 18 secondary end points, of which 5 are reported in this article: 28-day mortality, 6-month Disability Rating Scale score (range, 0 [no disability] to 30 [death]), progression of intracranial hemorrhage, incidence of seizures, and incidence of thromboembolic events. Results Among 1063 participants, a study drug was not administered to 96 randomized participants and 1 participant was excluded, resulting in 966 participants in the analysis population (mean age, 42 years; 255 [74%] male participants; mean Glasgow Coma Scale score, 8). Of these participants, 819 (84.8%) were available for primary outcome analysis at 6-month follow-up. The primary outcome occurred in 65% of patients in the tranexamic acid groups vs 62% in the placebo group (difference, 3.5%; [90% 1-sided confidence limit for benefit, -0.9%]; P = .16; [97.5% 1-sided confidence limit for harm, 10.2%]; P = .84). There was no statistically significant difference in 28-day mortality between the tranexamic acid groups vs the placebo group (14% vs 17%; difference, -2.9% [95% CI, -7.9% to 2.1%]; P = .26), 6-month Disability Rating Scale score (6.8 vs 7.6; difference, -0.9 [95% CI, -2.5 to 0.7]; P = .29), or progression of intracranial hemorrhage (16% vs 20%; difference, -5.4% [95% CI, -12.8% to 2.1%]; P = .16). Conclusions and Relevance Among patients with moderate to severe TBI, out-of-hospital tranexamic acid administration within 2 hours of injury compared with placebo did not significantly improve 6-month neurologic outcome as measured by the Glasgow Outcome Scale-Extended. Trial Registration ClinicalTrials.gov Identifier: NCT01990768.

中文翻译：

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院外氨甲环酸与安慰剂对中度或重度创伤性脑损伤患者 6 个月功能性神经系统预后的影响

重要性 创伤性脑损伤 (TBI) 是外伤导致的死亡和残疾的主要原因。早期给予氨甲环酸可能有益于 TBI 患者。目的 确定在伤后 2 小时内在院外环境中开始的氨甲环酸治疗是否能改善中度或重度 TBI 患者的神经系统预后。设计、设置和参与者 2015 年 5 月至 2017 年 11 月在美国和加拿大的 20 个创伤中心和 39 个紧急医疗服务机构进行的多中心、双盲、随机临床试验。符合条件的参与者 (N = 1280) 包括院外15 岁或以上的 TBI 患者，格拉斯哥昏迷量表评分为 12 或更低，收缩压为 90 mmHg 或更高。干预 评估了三种干预措施，在 TBI 后 2 小时内开始治疗：院外传明酸 (1 g) 推注和院内传明酸 (1 g) 8 小时输注（推注维持组；n = 312）、院外传明酸 (2 g) 推注和在- 医院安慰剂 8 小时输注（仅推注组；n = 345），以及院外安慰剂推注和院内安慰剂 8 小时输注（安慰剂组；n = 309）。主要结果和措施 与安慰剂组相比，氨甲环酸联合组的主要结果是 6 个月时的神经功能良好（格拉斯哥结果量表扩展评分 >4 [中度残疾或恢复良好]）。不对称显着性阈值被设定为 0.1 的收益和 0.025 的伤害。有 18 个次要终点，其中 5 个在本文中报告：28 天死亡率，6 个月残疾评定量表评分（范围，0 [无残疾] 至 30 [死亡]），颅内出血的进展、癫痫发作的发生率和血栓栓塞事件的发生率。结果 在 1063 名参与者中，96 名随机参与者未使用研究药物，1 名参与者被排除在外，导致分析人群中有 966 名参与者（平均年龄 42 岁；255 名 [74%] 男性参与者；平均格拉斯哥昏迷量表评分， 8). 在这些参与者中，819 人 (84.8%) 在 6 个月的随访中可用于主要结果分析。主要结果发生在氨甲环酸组的 65% 与安慰剂组的 62%（差异，3.5%；[90% 单侧获益置信限，-0.9%]；P = .16；[97.5 % 1 边伤害置信限，10.2%]；P = .84）。氨甲环酸组与安慰剂组之间的 28 天死亡率无统计学差异（14% 与 17%；差异，-2.9% [95% CI，-7.9% 至 2.1%]；P = .26)、6 个月残疾评定量表评分（6.8 对 7.6；差异，-0.9 [95% CI，-2.5 至 0.7]；P = .29）或颅内出血进展（16% 对 20% ；差异，-5.4% [95% CI，-12.8% 至 2.1%]；P = .16）。结论和相关性 在中度至重度 TBI 患者中，与安慰剂相比，在受伤后 2 小时内院外给予氨甲环酸并没有显着改善 6 个月的神经系统结局，如格拉斯哥结局量表扩展所测量的。试验注册 ClinicalTrials.gov 标识符：NCT01990768。结论和相关性 在中重度 TBI 患者中，与安慰剂相比，在受伤后 2 小时内院外给予氨甲环酸并没有显着改善 6 个月的神经系统结局，这通过格拉斯哥结局量表扩展来衡量。试验注册 ClinicalTrials.gov 标识符：NCT01990768。结论和相关性 在中重度 TBI 患者中，与安慰剂相比，在受伤后 2 小时内院外给予氨甲环酸并没有显着改善 6 个月的神经系统结局，这通过格拉斯哥结局量表扩展来衡量。试验注册 ClinicalTrials.gov 标识符：NCT01990768。