高剂量 24 小时输注氨甲环酸对急性胃肠出血患者死亡和血栓栓塞事件的影响（HALT-IT）：一项国际随机、双盲、安慰剂对照试验。

Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial.

出版信息

Lancet. 2020 Jun 20;395(10241):1927-1936. doi: 10.1016/S0140-6736(20)30848-5.

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7306161/

Abstract

BACKGROUND

Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding.

METHODS

We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124.

FINDINGS

Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82-1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98).

INTERPRETATION

We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial.

FUNDING

UK National Institute for Health Research Health Technology Assessment Programme.

摘要

背景

氨甲环酸可减少创伤患者的手术出血并降低因出血导致的死亡。小型试验的荟萃分析表明，氨甲环酸可能会降低胃肠道出血导致的死亡。我们旨在评估氨甲环酸在胃肠道出血患者中的作用。

方法

我们在 15 个国家的 164 家医院进行了一项国际性、多中心、随机、安慰剂对照试验。如果负责的临床医生不确定是否使用氨甲环酸，则招募患者；年龄大于其所在国家规定的成年年龄（16 岁或 18 岁以上）；且有明显（定义为有出血死亡风险）上或下胃肠道出血。患者通过从一个包含 8 个包装的盒子中选择一个编号的治疗包进行随机分组，这些包装除了编号外完全相同。患者接受负荷剂量 1 g 氨甲环酸，加入 100 mL 0.9%氯化钠输注袋中，缓慢静脉注射 10 min，然后给予维持剂量 3 g 氨甲环酸加入 1 L 任何等渗静脉溶液中，以 125 mg/h 输注 24 h，或安慰剂（0.9%氯化钠）。患者、护理人员和评估结局的人员对分配情况进行了盲法。主要结局是随机分组后 5 天内因出血导致的死亡；分析排除了既未接受分配治疗剂量的患者，也排除了死亡结局数据不可用的患者。该试验在 Current Controlled Trials、ISRCTN11225767 和 ClinicalTrials.gov 上注册，编号分别为 NCT01658124。

结果

在 2013 年 7 月 4 日至 2019 年 6 月 21 日期间，我们随机分配了 12009 名患者接受氨甲环酸（5994 名，49.9%）或匹配的安慰剂（6015 名，50.1%），其中 11952 名（99.5%）接受了分配治疗的首剂。随机分组后 5 天内因出血导致的死亡发生在氨甲环酸组的 5956 名患者中 222 例（4%）和安慰剂组的 5981 名患者中 226 例（4%）（风险比[RR]0.99，95%CI 0.82-1.18）。氨甲环酸组和安慰剂组的动脉血栓栓塞事件（心肌梗死或中风）相似（氨甲环酸组 5952 名患者中有 42 例[0.7%]，安慰剂组 5977 名患者中有 46 例[0.8%]；0.92；0.60 至 1.39）。氨甲环酸组的静脉血栓栓塞事件（深静脉血栓形成或肺栓塞）高于安慰剂组（氨甲环酸组 5952 名患者中有 48 例[0.8%]，安慰剂组 5977 名患者中有 26 例[0.4%]；RR 1.85；95%CI 1.15 至 2.98）。