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

Summary

In a multicentre, double-blind phase 3 RCT of 1106 adults with sepsis, thymosin α1 did not reduce 28-day all-cause mortality versus placebo (HR 0.99). No secondary or safety endpoints differed; age and diabetes showed interaction signals, which are hypothesis-generating.

Key Findings

• 28-day all-cause mortality was 23.4% with thymosin α1 vs 24.1% with placebo (HR 0.99, 95% CI 0.77–1.27; P=0.93).
• No significant differences in secondary or safety outcomes between groups.
• Pre-specified subgroup interactions: age (<60 years HR 1.67 vs ≥60 years HR 0.81; interaction P=0.01) and diabetes (diabetes HR 0.58 vs no diabetes HR 1.16; interaction P=0.04).
• Intervention: subcutaneous thymosin α1 every 12 hours for 7 days.

Clinical Implications

Routine use of thymosin α1 for adult sepsis should be avoided. If considered, it should be restricted to clinical trials with immunophenotyping and pre-specified enrichment strategies.

Limitations

• Single-country study (China), potentially affecting generalizability
• Subgroup findings may be due to chance; lack of biomarker-guided patient selection

Future Directions

Design immunophenotype-enriched trials of sepsis immunotherapies; evaluate adaptive designs and early biological endpoints to detect subgroup benefits.