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[JAMA在线发表]: SCARLET研究显示,重组人可溶性血栓调节蛋白不能降低脓毒症相关凝血病患者的病死率
2019年05月21日 时讯速递, 进展交流 暂无评论

Original Investigation Caring for the Critically Ill PatientMay 19, 2019

Effect of a Recombinant Human Soluble Thrombomodulin on Mortality in Patients With Sepsis-Associated Coagulopathy: The SCARLET Randomized Clinical Trial

Jean-Louis Vincent, Bruno Francois, Igor Zabolotskikh, et al

JAMA. Published online May 19, 2019. doi:10.1001/jama.2019.5358

Abstract

Importance 背景

Previous research suggested that soluble human recombinant thrombomodulin may reduce mortality among patients with sepsis-associated coagulopathy.

既往研究提示,可溶性人重组血栓调节蛋白能够降低脓毒症相关凝血病患者的病死率。

Objective 目的

To determine the effect of human recombinant thrombomodulin vs placebo on 28-day all-cause mortality among patients with sepsis-associated coagulopathy.

确定人重组血栓调节蛋白与安慰剂对脓毒症相关凝血病患者28天全因病死率的影响。

Design, Setting, and Participants 试验设计,场景及研究对象

The SCARLET trial was a randomized, double-blind, placebo-controlled, multinational, multicenter phase 3 study conducted in intensive care units at 159 sites in 26 countries. All adult patients admitted to one of the participating intensive care units between October 2012 and March 2018 with sepsis-associated coagulopathy and concomitant cardiovascular and/or respiratory failure, defined as an international normalized ratio greater than 1.40 without other known etiology and a platelet count in the range of 30 to 150 × 109/L or a greater than 30% decrease in platelet count within 24 hours, were considered for inclusion. The final date of follow-up was February 28, 2019.

SCARLET试验是一项随机双盲安慰剂对照,多国多中心3期临床试验。试验在26个国家159个ICU进行。2012年10月至2018年3月间,参研中心收治的所有成年患者若满足脓毒症相关凝血病(定义为INR > 1.40且无其他已知病因,血小板计数30 - 150 x 109/L或24小时内下降> 30%)及心血管和(或)呼吸功能衰竭可以入选。最后随访日期为2019年2月28日。

Interventions 干预措施

Patients with sepsis-associated coagulopathy were randomized and treated with an intravenous bolus or a 15-minute infusion of thrombomodulin (0.06 mg/kg/d [maximum, 6 mg/d]; n = 395) or matching placebo (n = 405) once daily for 6 days.

脓毒症相关凝血病患者接受随机分组,静脉推注或15分钟内输注血栓调节蛋白(0.06 mg/kg/d [最大剂量, 6 mg/d]; n = 395) 或匹配安慰剂 (n = 405),每日1次,疗程为6天。

Main Outcome and Measures 主要预后指标

The primary end point was 28-day all-cause mortality.

主要预后终点为28天全因病死率。

Results 结果

Among 816 randomized patients, 800 (mean age, 60.7 years; 437 [54.6%] men) completed the study and were included in the full analysis set. In these patients, the 28-day all-cause mortality rate was not statistically significantly different between the thrombomodulin group and the placebo group (106 of 395 patients [26.8%] vs 119 of 405 patients [29.4%], respectively; P = .32). The absolute risk difference was 2.55% (95% CI, −3.68% to 8.77%). The incidence of serious major bleeding adverse events (defined as any intracranial hemorrhage; life-threatening bleeding; or bleeding event classified as serious by the investigator, with administration of at least 1440 mL [typically 6 units] of packed red blood cells over 2 consecutive days) was 23 of 396 patients (5.8%) in the thrombomodulin group and 16 of 404 (4.0%) in the placebo group.

共有816名患者接受随机分组,800名(平均年龄,60.7岁;437名 [54.6%]为男性)患者完成试验,纳入最后分析数据集。这些患者中,血栓调节蛋白组与安慰剂组28天全因病死率无统计学显著差异(106/395 [26.8%] vs 119/405 [29.4%]; P = .32)。绝对风险差异为2.55% (95% CI, −3.68% to 8.77%)。血栓调节蛋白组严重大出血(定义为颅内出血;致命性出血;或研究者认定的严重出血事件,连续2天内输注至少1440 mL [6个单位] 浓缩红细胞)的发生率为23/396 (5.8%),安慰剂组为 16/404 (4.0%)。

Conclusions and Relevance 结论与意义

Among patients with sepsis-associated coagulopathy, administration of a human recombinant thrombomodulin, compared with placebo, did not significantly reduce 28-day all-cause mortality.

对于脓毒症相关凝血病患者,与安慰剂对照相比,输注人重组血栓调节蛋白不能显著降低28天全因病死率。

Trial Registration 试验注册

ClinicalTrials.gov Identifier: NCT01598831

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