胸腺肽α1治疗脓毒症的疗效和安全性研究（TESTS）：多中心、双盲、随机、安慰剂对照3期试验
The efficacy and safety of thymosin α1 for sepsis (TESTS): multicentre, double blinded, randomised, placebo controlled, phase 3 trial.
作者信息
Wu Jianfeng, Pei Fei, Zhou Lixin, Li Weiqin, Sun Renhua, Li Yimin, Wang Zheng, He Zhijie, Zhang Xiaofei, Jin Xiaodong, Long Yun, Cui Wei, Wang Chunting, Chen Erzhen, Zeng Jun, Yan Jing, Lin Qinhan, Zhou Feihu, Huang Lei, Shang You, Duan Meili, Zheng Wei, Zhu Duming, Kou Qiuye, Zhang Shihong, Liu Yin, Yao Chen, Shang Meixia, Peng Sui, Zhou Qian, Cheng Kar Keung, Guan Xiangdong
机构信息
Department of Critical Care Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong province, China.
Guangdong Clinical Research Center for Critical Care Medicine, Guangzhou, Guangdong province, China.
出版信息
BMJ. 2025 Jan 15;388:e082583. doi: 10.1136/bmj-2024-082583.
OBJECTIVE
To evaluate whether the immunomodulatory drug thymosin α1 reduces mortality in adults with sepsis.
DESIGN
Multicentre, double blinded, placebo controlled phase 3 trial.
SETTING
22 centres in China, September 2016 to December 2020.
PARTICIPANTS
1106 adults aged 18-85 years with a diagnosis of sepsis according to sepsis-3 criteria and randomly assigned in a 1:1 ratio to receive thymosin α1 (n=552) or placebo (n=554). A stratified block method was used for randomisation, and participants were stratified by age (<60 and ≥60 years) and centre.
INTERVENTIONS
Subcutaneous injection of thymosin α1 or placebo every 12 hours for seven days unless discontinued owing to discharge from the intensive care unit, death, or withdrawal of consent.
MAIN OUTCOME MEASURE
The primary outcome was 28 day all cause mortality after randomisation. All analyses were based on a modified intention-to-treat set, including participants who received at least one dose of study drug.
RESULTS
Of 1106 adults with sepsis enrolled in the study, 1089 were included in the modified intention-to-treat analyses (thymosin α1 group n=542, placebo group n=547). 28 day all cause mortality occurred in 127 participants (23.4%) in the thymosin α1 group and 132 (24.1%) in the placebo group (hazard ratio 0.99, 95% confidence interval 0.77 to 1.27; P=0.93 with log-rank test). No secondary or safety outcome differed statistically significantly between the two groups. The prespecified subgroup analysis showed a potential differential effect of thymosin α1 on the primary outcome based on age (<60 years: hazard ratio 1.67, 1.04 to 2.67; ≥60 years: 0.81, 0.61 to 1.09; P for interaction=0.01) and diabetes (diabetes: 0.58, 0.35 to 0.99; no diabetes: 1.16, 0.87 to 1.53; P for interaction=0.04).
CONCLUSIONS
This trial found no clear evidence to suggest that thymosin α1 decreases 28 day all cause mortality in adults with sepsis.
TRIAL REGISTRATION
ClinicalTrials.gov NCT02867267.
目的
评估免疫调节药物胸腺肽α1是否能降低脓毒症成年患者的死亡率。
设计
多中心、双盲、安慰剂对照3期试验。
地点
中国22个中心，2016年9月至2020年12月。
参与者
1106名年龄在18 - 85岁之间、根据脓毒症-3标准诊断为脓毒症的成年人，按1:1比例随机分配接受胸腺肽α1（n = 552）或安慰剂（n = 554）。采用分层区组法进行随机分组，参与者按年龄（<60岁和≥60岁）和中心分层。
干预措施
每12小时皮下注射胸腺肽α1或安慰剂，共7天，除非因从重症监护病房出院、死亡或撤回同意书而停药。
主要结局指标
主要结局为随机分组后28天全因死亡率。所有分析均基于改良意向性分析集，包括接受至少一剂研究药物的参与者。
结果
在纳入研究的1106名脓毒症成年患者中，1089名纳入改良意向性分析（胸腺肽α1组n = 542，安慰剂组n = 547）。胸腺肽α1组127名参与者（23.4%）发生28天全因死亡，安慰剂组132名（24.1%）（风险比0.99，95%置信区间0.77至1.27；对数秩检验P = 0.93）。两组间次要结局或安全性结局无统计学显著差异。预先设定的亚组分析显示，胸腺肽α1对主要结局的影响可能因年龄（<60岁：风险比1.67，1.04至2.67；≥60岁：0.81，0.61至1.09；交互作用P = 0.01）和糖尿病（糖尿病：0.58，0.35至0.99；无糖尿病：1.16，0.87至1.53；交互作用P = 0.04）而异。
结论
本试验未发现明确证据表明胸腺肽α1可降低脓毒症成年患者28天全因死亡率。
试验注册号
ClinicalTrials.gov NCT02867267。
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