超早期氨甲环酸治疗蛛网膜下腔出血后试验（ULTRA）：一项随机对照试验。

Ultra-early tranexamic acid after subarachnoid haemorrhage (ULTRA): a randomised controlled trial.

机构信息

Department of Neurosurgery, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.

Department of Neurosurgery, Clinical Neuroscience Center, University Hospital Zurich, Zurich, Switzerland.

出版信息

Lancet. 2021 Jan 9;397(10269):112-118. doi: 10.1016/S0140-6736(20)32518-6. Epub 2020 Dec 23.

DOI:10.1016/S0140-6736(20)32518-6

PMID:33357465

Abstract

BACKGROUND

In patients with aneurysmal subarachnoid haemorrhage, short-term antifibrinolytic therapy with tranexamic acid has been shown to reduce the risk of rebleeding. However, whether this treatment improves clinical outcome is unclear. We investigated whether ultra-early, short-term treatment with tranexamic acid improves clinical outcome at 6 months.

METHODS

In this multicentre prospective, randomised, controlled, open-label trial with masked outcome assessment, adult patients with spontaneous CT-proven subarachnoid haemorrhage in eight treatment centres and 16 referring hospitals in the Netherlands were randomly assigned to treatment with tranexamic acid in addition to care as usual (tranexamic acid group) or care as usual only (control group). Tranexamic acid was started immediately after diagnosis in the presenting hospital (1 g bolus, followed by continuous infusion of 1 g every 8 h, terminated immediately before aneurysm treatment, or 24 h after start of the medication, whichever came first). The primary endpoint was clinical outcome at 6 months, assessed by the modified Rankin Scale, dichotomised into a good (0-3) or poor (4-6) clinical outcome. Both primary and safety analyses were according to intention to treat. This trial is registered at ClinicalTrials.gov, NCT02684812.

FINDINGS

Between July 24, 2013, and July 29, 2019, we enrolled 955 patients; 480 patients were randomly assigned to tranexamic acid and 475 patients to the control group. In the intention-to-treat analysis, good clinical outcome was observed in 287 (60%) of 475 patients in the tranexamic acid group, and 300 (64%) of 470 patients in the control group (treatment centre adjusted odds ratio 0·86, 95% CI 0·66-1·12). Rebleeding after randomisation and before aneurysm treatment occurred in 49 (10%) patients in the tranexamic acid and in 66 (14%) patients in the control group (odds ratio 0·71, 95% CI 0·48-1·04). Other serious adverse events were comparable between groups.

INTERPRETATION

In patients with CT-proven subarachnoid haemorrhage, presumably caused by a ruptured aneurysm, ultra-early, short-term tranexamic acid treatment did not improve clinical outcome at 6 months, as measured by the modified Rankin Scale.

FUNDING

Fonds NutsOhra.

摘要

背景

在蛛网膜下腔出血的患者中，短期使用氨甲环酸的抗纤维蛋白溶解疗法已被证明可降低再出血的风险。但是，这种治疗方法是否可以改善临床预后尚不清楚。我们研究了超早期、短期使用氨甲环酸是否可以改善 6 个月时的临床预后。

方法

在这项多中心前瞻性、随机、对照、开放性标记试验中，使用了盲法结局评估，将荷兰 8 个治疗中心和 16 家转诊医院的自发性 CT 证实的蛛网膜下腔出血成年患者随机分配到氨甲环酸加常规治疗组（氨甲环酸组）或仅常规治疗组（对照组）。氨甲环酸在出现医院（1 g 推注，随后每 8 小时持续输注 1 g，在进行动脉瘤治疗之前立即终止，或在开始用药 24 小时后终止，以先发生者为准）诊断后立即开始治疗。主要终点是改良Rankin 量表评估的 6 个月时的临床预后，分为良好（0-3 分）或不良（4-6 分）的临床预后。主要和安全性分析均按意向治疗进行。该试验在 ClinicalTrials.gov 注册，NCT02684812。

结果

在 2013 年 7 月 24 日至 2019 年 7 月 29 日期间，我们共纳入了 955 名患者；480 名患者被随机分配到氨甲环酸组，475 名患者分配到对照组。在意向治疗分析中，氨甲环酸组的 475 名患者中有 287 名（60%）和对照组的 470 名患者中有 300 名（64%）的临床预后良好（治疗中心调整的比值比为 0.86，95%CI 0.66-1.12）。在随机分组后且在进行动脉瘤治疗前，氨甲环酸组有 49 名（10%）患者和对照组有 66 名（14%）患者再次出血（比值比为 0.71，95%CI 0.48-1.04）。两组的其他严重不良事件相当。