Clinical Trials Unit, London School of Hygiene & Tropical Medicine, London, UK.
RoadPeace, London, UK.
Health Technol Assess. 2021 Apr;25(26):1-76. doi: 10.3310/hta25260.
Tranexamic acid safely reduces mortality in traumatic extracranial bleeding. Intracranial bleeding is common after traumatic brain injury and can cause brain herniation and death. We assessed the effects of tranexamic acid in traumatic brain injury patients.
To assess the effects of tranexamic acid on death, disability and vascular occlusive events in traumatic brain injury patients. We also assessed cost-effectiveness.
Randomised trial and economic evaluation. Patients were assigned by selecting a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients, caregivers and those assessing outcomes were masked to allocation. All analyses were by intention to treat. We assessed the cost-effectiveness of tranexamic acid versus no treatment from a UK NHS perspective using the trial results and a Markov model.
175 hospitals in 29 countries.
Adults with traumatic brain injury within 3 hours of injury with a Glasgow Coma Scale score of ≤ 12 or any intracranial bleeding on computerised tomography scan, and no major extracranial bleeding, were eligible.
Tranexamic acid (loading dose 1 g over 10 minutes then infusion of 1 g over 8 hours) or matching placebo.
Head injury death in hospital within 28 days of injury in patients treated within 3 hours of injury. Secondary outcomes were early head injury deaths, all-cause and cause-specific mortality, disability, vascular occlusive events, seizures, complications and adverse events.
Among patients treated within 3 hours of injury ( = 9127), the risk of head injury death was 18.5% in the tranexamic acid group versus 19.8% in the placebo group (855/4613 vs. 892/4514; risk ratio 0.94, 95% confidence interval 0.86 to 1.02). In a prespecified analysis excluding patients with a Glasgow Coma Scale score of 3 or bilateral unreactive pupils at baseline, the results were 12.5% in the tranexamic acid group versus 14.0% in the placebo group (485/3880 vs. 525/3757; risk ratio 0.89, 95% confidence interval 0.80 to 1.00). There was a reduction in the risk of head injury death with tranexamic acid in those with mild to moderate head injury (166/2846 vs. 207/2769; risk ratio 0.78, 95% confidence interval 0.64 to 0.95), but in those with severe head injury (689/1739 vs. 685/1710; risk ratio 0.99, 95% confidence interval 0.91 to 1.07) there was no apparent reduction (-value for heterogeneity = 0.030). Early treatment was more effective in mild and moderate head injury ( = 0.005), but there was no obvious impact of time to treatment in cases of severe head injury ( = 0.73). The risk of disability, vascular occlusive events and seizures was similar in both groups. Tranexamic acid is highly cost-effective for mild and moderate traumatic brain injury (base case of £4288 per quality-adjusted life-year gained).
Early tranexamic acid treatment reduces head injury deaths. Treatment is cost-effective for patients with mild or moderate traumatic brain injury, or those with both pupils reactive.
Further trials should examine early tranexamic acid treatment in mild head injury. Research on alternative routes of administration is needed.
Time to treatment may have been underestimated.
Current Controlled Trials ISRCTN15088122, ClinicalTrials.gov NCT01402882, EudraCT 2011-003669-14, Pan African Clinical Trial Registry PACTR20121000441277.
The project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in ; Vol. 25, No. 26. See the NIHR Journals Library website for further project information. In addition, funding was provided by JP Moulton Charitable Trust, Joint Global Health Trials (Medical Research Council, Department for International Development and the Wellcome Trust). This project was funded by the NIHR Global Health Trials programme.
氨甲环酸可安全降低创伤性颅外出血患者的死亡率。创伤性脑损伤后常发生颅内出血，并可导致脑疝和死亡。我们评估了氨甲环酸在创伤性脑损伤患者中的作用。
评估氨甲环酸对创伤性脑损伤患者死亡、残疾和血管闭塞事件的影响。我们还评估了成本效益。
随机试验和经济评估。通过从包含 8 个包装的盒子中选择一个编号的治疗包来分配患者，除了包装编号外，这些包装完全相同。患者、护理人员和评估结果的人员对分配情况不知情。所有分析均基于意向治疗。我们使用试验结果和马尔可夫模型从英国国民健康保险制度的角度评估了氨甲环酸与无治疗相比的成本效益。
29 个国家的 175 家医院。
损伤后 3 小时内、格拉斯哥昏迷量表评分≤12 分或计算机断层扫描显示任何颅内出血、无重大颅外出血的成年创伤性脑损伤患者。
氨甲环酸（负荷剂量 1 g 静脉滴注 10 分钟，然后输注 1 g 持续 8 小时）或匹配的安慰剂。
损伤后 28 天内院内创伤性脑损伤死亡。次要结局指标包括早期创伤性脑损伤死亡、全因和病因特异性死亡率、残疾、血管闭塞事件、癫痫发作、并发症和不良事件。
在损伤后 3 小时内接受治疗的患者中（n=9127），氨甲环酸组的创伤性脑损伤死亡风险为 18.5%，安慰剂组为 19.8%（855/4613 与 892/4514；风险比 0.94，95%置信区间 0.86 至 1.02）。在一项预先指定的排除基线格拉斯哥昏迷量表评分为 3 分或双侧无反应瞳孔的患者分析中，氨甲环酸组的结果为 12.5%，安慰剂组为 14.0%（485/3880 与 525/3757；风险比 0.89，95%置信区间 0.80 至 1.00）。在轻度至中度创伤性脑损伤患者中，氨甲环酸降低了创伤性脑损伤死亡的风险（166/2846 与 207/2769；风险比 0.78，95%置信区间 0.64 至 0.95），但在重度创伤性脑损伤患者中（689/1739 与 685/1710；风险比 0.99，95%置信区间 0.91 至 1.07），未见明显减少（异质性检验值=0.030）。轻度和中度创伤性脑损伤的早期治疗更为有效（P=0.005），但重度创伤性脑损伤患者的治疗时间无明显影响（P=0.73）。两组的残疾、血管闭塞事件和癫痫发作风险相似。氨甲环酸对轻度和中度创伤性脑损伤具有高度成本效益（获得每质量调整生命年的成本为 4288 英镑）。
早期氨甲环酸治疗可降低创伤性脑损伤死亡。对于轻度或中度创伤性脑损伤或双侧瞳孔反应性的患者，治疗具有成本效益。
应进一步研究轻度创伤性脑损伤患者的早期氨甲环酸治疗。需要研究替代给药途径。
治疗时间可能被低估。
当前对照试验 ISRCTN85112024，临床试验.gov NCT01402882，EudraCT 2011-003669-14，泛非临床试验登记处 PACTR20121000441277。
该项目由英国国家卫生研究所（NIHR）卫生技术评估计划资助，将在 ; Vol. 25, No. 26 中全文发表。请访问 NIHR 期刊库网站以获取更多项目信息。此外，JP Moulton 慈善信托基金、全球卫生试验联合组织（医学研究理事会、国际发展部和惠康信托基金）也为该项目提供了资金。该项目由英国国民健康保险制度全球卫生试验计划资助。
