The efficacy and safety of thymosin α1 for sepsis (TESTS): multicentre, double blinded, randomised, placebo controlled, phase 3 trial.
Thymosin α1 did not show a significant reduction in 28-day mortality for adults with sepsis, with a hazard ratio of 0.99, indicating no clear benefit.
Where it sits
this study against the rest of the thymosin alpha-1 corpusSummary and findings
This phase 3 trial evaluated the efficacy of thymosin α1 in reducing mortality among 1106 adults with sepsis. Participants were randomly assigned to receive either thymosin α1 (n=552) or placebo (n=554) via subcutaneous injection every 12 hours for seven days. The study found no significant difference in 28-day all-cause mortality between the two groups.
Abstract
<h4>Objective</h4>To evaluate whether the immunomodulatory drug thymosin α1 reduces mortality in adults with sepsis.<h4>Design</h4>Multicentre, double blinded, placebo controlled phase 3 trial.<h4>Setting</h4>22 centres in China, September 2016 to December 2020.<h4>Participants</h4>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.<h4>Interventions</h4>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.<h4>Main outcome measure</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>This trial found no clear evidence to suggest that thymosin α1 decreases 28 day all cause mortality in adults with sepsis.<h4>Trial registration</h4>ClinicalTrials.gov NCT02867267.
Background
The paper addresses the clinical question of whether thymosin α1 can improve outcomes in patients with sepsis, a condition associated with high morbidity and mortality. Prior studies have suggested potential benefits of thymosin α1 in immune modulation, but robust evidence from large-scale trials is lacking. This study aims to fill that gap by providing data from a phase 3 trial.
Methods
The study employed a multicentre, double-blinded, randomized, placebo-controlled design. The population included patients diagnosed with sepsis, although specific inclusion criteria and demographics are not reported in the abstract. The dose and duration of thymosin α1 administration are not specified, nor are the primary and secondary outcome measures detailed.
Results
Not reported in abstract.
Interpretation
Without specific results, it is challenging to compare this study's findings to existing literature or assess the clinical significance of any observed effects. The lack of reported data raises concerns about the robustness of the conclusions that can be drawn. Potential confounds include the absence of detailed methodology and results, which limits the ability to evaluate the implications for clinical practice.
Key findings
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Limitations
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