The efficacy and safety of thymosin α1 for sepsis (TESTS): multicentre, double blinded, randomised, placebo controlled, phase 3 trial.

Methods

Multicentre, double blinded, placebo controlled phase 3 trial.

多中心、双盲、安慰剂对照的III期临床试验。

22 centres in China, September 2016 to December 2020.

22个中心在中国，2016年9月至2020年12月。

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).

1106名年龄在18-85岁之间的成人，根据sepsis-3标准诊断为败血症，并以1:1的比例随机分配接受胸腺肽α1（n=552）或安慰剂（n=554）。

A stratified block method was used for randomisation, and participants were stratified by age (<60 and ≥60 years) and centre.

使用了分层区组方法进行随机分组，参与者按年龄（<60岁和≥60岁）和研究中心进行分层。

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.

除非因出院、死亡或撤回同意而中断，否则每12小时皮下注射胸腺α1或安慰剂，连续七天。

main_outcome_measure

The primary outcome was 28 day all cause mortality after randomisation.

主要结果是随机化后28天的全因死亡率。

All analyses were based on a modified intention-to-treatset, including participants who received at least one dose of study drug.

所有分析均基于修改后的意向治疗集，包括至少接受一剂研究药物的参与者。

Results

Of 1106 adults with sepsis enrolled in the study, 1089 were included in the modified intention-to-treatanalyses (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 ratio0.99, 95% confidence interval0.77 to 1.27; P=0.93 with log-rank test).

在研究中纳入的1106名成人脓毒症患者中，有1089名被纳入修改后的意向治疗分析（胸腺肽α1组n=542，安慰剂组n=547）。28天全因死亡发生在胸腺肽α1组的127名参与者（23.4%）和安慰剂组的132名（24.1%）中（风险比0.99，95%置信区间0.77至1.27；使用对数秩检验的P=0.93）。

No secondary or safety outcome differed statistically significantly between the two groups.

两组之间没有次要或安全性结果在统计学上有显著差异。

The prespecified subgroup analysis showed a potential differential effect of thymosin α1 on the primary outcome based on age (<60 years: hazard ratio1.67, 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).

预先设定的亚组分析显示，胸腺肽α1对主要结果的影响可能基于年龄（<60岁：风险比1.67，95%置信区间1.04至2.67；≥60岁：0.81，95%置信区间0.61至1.09；交互作用P值=0.01）和糖尿病（糖尿病患者：0.58，95%置信区间0.35至0.99；无糖尿病患者：1.16，95%置信区间0.87至1.53；交互作用P值=0.04）。

Conclusions

This trial found no clear evidence to suggest that thymosin α1 decreases 28 day all cause mortality in adults with sepsis.

该试验未发现胸腺肽α1能显著降低成人败血症患者28天全因死亡率的明确证据。

trial_registration

ClinicalTrials.gov NCT02867267.

ClinicalTrials.gov NCT02867267。