Tranexamic acid in patients with intracerebral haemorrhage (STOP-AUST): a multicentre, randomised, placebo-controlled, phase 2 trial
Tranexamic acid in patients with intracerebral haemorrhage (STOP-AUST): a multicentre, randomised, placebo-controlled, phase 2 trial
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DOI：
10.1016/s1474-4422(20)30369-0
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发表时间：
2020-12-01
期刊：
影响因子：
48
通讯作者：
Davis, Stephen M.
中科院分区：
文献类型：
--
作者：
Meretoja, Atte;Yassi, Nawaf;Davis, Stephen M.
背景尽管脑出血导致全世界5%的死亡，但除了卒中单元护理外，几乎没有基于证据的治疗策略。氨甲环酸减少出血的条件，如急性创伤和月经。我们的目的是评估是否氨甲环酸减少急性intracerebral hemorrhage.Methods患者的颅内出血增长，我们做了一个前瞻性，双盲，随机，安慰剂对照，促发剂主导的，2期试验在13个中风中心在澳大利亚，芬兰和台湾。如果患者年龄≥ 18岁，24 h时急性脑出血符合临床标准（例如，格拉斯哥昏迷量表评分>7，脑出血量33%相对值或>6 mL绝对值），则患者合格。在意向治疗人群中进行了主要和安全性分析。该试验在ClinicalTrials.gov（NCT 01702636）上注册。结果在2013年3月1日至2019年8月13日期间，我们招募了100名参与者，并将其随机分配到氨甲环酸组（n=50）或安慰剂组（n=50）。基线时中位年龄为71岁（IQR 57-79），中位脑出血量为14.6 mL（7.9-32.7）。两组之间的主要结局无差异：安慰剂组26例（52%）患者和氨甲环酸组22例（44%）患者发生脑出血增长（比值比[OR] 0.72 [95%CI 0.32-1.59]，p=0.41）。没有证据表明两组之间死亡或发生血栓栓塞并发症的患者比例存在差异：安慰剂组8例（16%）vs氨甲环酸组13例（26%）死亡，2例（4%）vs 1例（2%）发生血栓栓塞并发症。没有死亡被认为与研究medication.Interpretation相关，我们的研究没有提供证据表明氨甲环酸可以防止脑出血的增长，虽然治疗是安全的，没有增加血栓栓塞并发症。更大规模的氨甲环酸试验，招募方法更简单，治疗窗更早，是合理的。
Background Despite intracerebral haemorrhage causing 5% of deaths worldwide, few evidence-based therapeutic strategies other than stroke unit care exist. Tranexamic acid decreases haemorrhage in conditions such as acute trauma and menorrhoea. We aimed to assess whether tranexamic acid reduces intracerebral haemorrhage growth in patients with acute intracerebral haemorrhage.Methods We did a prospective, double-blind, randomised, placebo-controlled, investigator-led, phase 2 trial at 13 stroke centres in Australia, Finland, and Taiwan. Patients were eligible if they were aged 18 years or older, had an acute intracerebral haemorrhage fulfilling clinical criteria (eg, Glasgow Coma Scale score of >7, intracerebral haemorrhage volume 33% relative or >6 mL absolute) at 24 h. The primary and safety analyses were done in the intention-to-treat population. The trial is registered at ClinicalTrials.gov (NCT01702636).Findings Between March 1, 2013, and Aug 13, 2019, we enrolled and randomly assigned 100 participants to the tranexamic acid group (n=50) or the placebo group (n=50). Median age was 71 years (IQR 57-79) and median intracerebral haemorrhage volume was 14.6 mL (7.9-32.7) at baseline. The primary outcome was not different between the two groups: 26 (52%) patients in the placebo group and 22 (44%) in the tranexamic acid group had intracerebral haemorrhage growth (odds ratio [OR] 0.72 [95% CI 0.32-1.59], p=0.41). There was no evidence of a difference in the proportions of patients who died or had thromboembolic complications between the groups: eight (16%) in the placebo group vs 13 (26%) in the tranexamic acid group died and two (4%) vs one (2%) had thromboembolic complications. None of the deaths was considered related to study medication.Interpretation Our study does not provide evidence that tranexamic acid prevents intracerebral haemorrhage growth, although the treatment was safe with no increase in thromboembolic complications. Larger trials of tranexamic acid, with simpler recruitment methods and an earlier treatment window, are justified.