Tranexamic acid versus placebo to prevent bleeding in patients with haematological malignancies and severe thrombocytopenia (TREATT): a randomised, double-blind, parallel, phase 3 superiority trial.

We aimed to assess the effect of tranexamic acid on preventing bleeding and the need for platelet transfusions.

我们旨在评估氨甲环酸对预防出血和减少血小板输注需求的影响。

Methods

TREATT was an international, randomised, double-blind, parallel, phase 3 superiority trial conducted at 27 haematology centres in Australia and the UK.

TREATT 是一项在澳大利亚和英国的27个血液学中心进行的国际性、随机、双盲、平行、第3阶段优势试验。

We enrolled adults (aged ≥18 years) receiving intensive chemotherapy or haematopoietic stem-cell transplantation for a haematological malignancy, with a platelet count of 10 × 109 platelets per L or less for 5 days or longer.

我们招募了接受强化化疗或造血干细胞移植治疗血液恶性肿瘤的成年人（年龄≥18岁），其血小板计数为10×10^9个血小板/L或更低，持续5天或更长时间。

Patients were randomly assigned (1:1) using block randomisation, stratified by site, to tranexamic acid (1 g every 8 h intravenously or 1·5g every 8 h orally) or placebo when their platelet count was less than 30 × 109 platelets per L.

患者按1:1的比例使用区块随机化方法进行随机分配，按地点分层，当他们的血小板计数少于30×10^9/L时，接受氨甲环酸（每8小时静脉注射1克或每8小时口服1.5克）或安慰剂治疗。

Treatment was continued until platelet recovery or day 30.

治疗持续至血小板恢复或第30天。

Prophylactic platelet transfusions were maintained as standard of care.

预防性血小板输注被维持为标准治疗。

The primary endpoint was the proportion of patients who died or had WHO grade 2 or higher bleeding up to day 30.

主要终点是截至第30天，患者死亡或出现WHO 2级或更高级别出血的比例。

A modified intention-to-treatpopulation including randomly assigned patients whose platelet count decreased to 30 × 109 platelets per L or less was used for analysis.

分析中使用了修改后的意向治疗人群，包括随机分配的患者，其血小板计数降低到每升30 × 10^9个血小板或更少。

This trial is registered with ClinicalTrials.gov (NCT03136445), ISRCTN (ISRCTN73545489), and the European Clinical Trials Register (EudraCT 2014-001513-35).

该试验已在ClinicalTrials.gov (NCT03136445)、ISRCTN (ISRCTN73545489)和欧洲临床试验登记处(EudraCT 2014-001513-35)注册。

Results

Between June 23, 2015, and Feb 17, 2022, 1736 patients were screened for eligibility, 616 of whom were enrolled and randomly assigned (310 to tranexamic acid and 306 to placebo). 19 participants were excluded from the modified intention-to-treatanalysis, leaving 300 participants in the tranexamic acid group and 297 in the placebo group.

2015年6月23日至2022年2月17日期间，共有1736名患者进行了资格筛查，其中616名被纳入并随机分配（310名接受氨甲环酸治疗，306名接受安慰剂）。在修改后的意向治疗分析中排除了19名参与者，最终氨甲环酸组有300名参与者，安慰剂组有297名。

Participant median age was 58 years (IQR 49-65), 380 (62%) of 616 participants were male, and 235 (38%) were female.

参与者的中位年龄为58岁（四分位数间距49-65岁），616名参与者中有380名（占62%）为男性，235名（占38%）为女性。

The proportion of participants who died or had WHO grade 2 or higher bleeding was 31·7% (90/298 [95% CI 26·6-37·4]) in the tranexamic acid group and 34·2% (98/295 [29·0-40·0]) in the placebo group (hazard ratio0·92 [95% CI 0·67-1·27]; p=0·62).

在氨甲环酸组中，死亡或出现2级或更高级别出血的参与者比例为31.7%（90/298 [95% 置信区间 26.6-37.4]），而在安慰剂组中这一比例为34.2%（98/295 [95% 置信区间 29.0-40.0]）（风险比为0.92 [95% 置信区间 0.67-1.27]；p=0.62）。

There were no differences in thrombotic events or veno-occlusive disease. 94 serious adverse events in 77 participants were reported up to day 60 in the tranexamic acid group and 103 events in 82 participants in the placebo group.

两组在血栓事件或静脉闭塞性疾病方面没有差异。在氨甲环酸组中，截至第60天，共有77名参与者报告了94起严重不良事件，而在安慰剂组中，有82名参与者报告了103起事件。

interpretation

There is insufficient evidence to support routine use of tranexamic acid to reduce bleeding in patients with haematological malignancies undergoing intensive chemotherapy.

目前的证据不足以支持在进行强化化疗的血液恶性肿瘤患者中常规使用氨甲环酸以减少出血。

funding

UK National Health Service Blood and Transplant and Australian National Health and Medical Research Council.

英国国家卫生服务血液和移植部门以及澳大利亚国家卫生和医学研究委员会。