Thymosin alpha-1 in sepsis: the TESTS phase 3 trial on the record
Prepared by: Research Desk. Sources are linked for verification.
Published 24 October 2026
At a glance
- Primary record: the TESTS trial (Wu et al., The BMJ, January 2025; registered as NCT02867267), a multicentre, double-blind, randomised, placebo-controlled phase 3 trial
- Scale: 1,106 adults with sepsis enrolled at 22 centres in China between September 2016 and December 2020; 1,089 were included in the modified ITT (mITT) analysis
- Main result: 28-day all-cause mortality was 23.4% in the thymosin alpha-1 group and 24.1% in the placebo group (hazard ratio 0.99, 95% CI 0.77 to 1.27, P=0.93)
- What came before: a smaller 2013 trial (ETASS) and several meta-analyses had pointed to lower mortality, but with wide confidence intervals
- US regulatory status: thymosin alpha-1 is not an FDA-approved drug, and FDA's safety-risk page lists it among bulk drug substances that may present significant safety risks in compounding
What thymosin alpha-1 is
Thymosin alpha-1 is a 28-residue peptide first isolated from calf thymus. Goldstein et al. (1977) reported its sequence in PNAS, describing a heat-stable, highly acidic polypeptide from the thymus extract known as thymosin fraction 5. The authors linked it to the regulation and differentiation of thymus-dependent lymphocytes (T cells).
Later laboratory work, summarised in a historical overview by Garaci (2007), reported effects on MHC class I and Toll-like receptor expression and on cytokine production. Those findings framed thymosin alpha-1 as an immune-regulating peptide and led to trials in sepsis, where immune suppression after the initial inflammatory phase is a recognised research question.
The earlier signal: ETASS (2013)
The first sizeable randomised trial in sepsis was ETASS, published in Critical Care (Wu et al., 2013; NCT00711620). It randomised 361 adults with severe sepsis at six teaching hospitals in China between 2008 and 2010 to thymosin alpha-1 or a control group, alongside conventional care.
- 28-day all-cause mortality was 26.0% with thymosin alpha-1 and 35.0% in the control group.
- The nonstratified analysis gave P=0.062 (log-rank P=0.049), and the relative risk of death was 0.74 (95% CI 0.54 to 1.02).
- The thymosin group showed a larger rise in monocyte HLA-DR, a marker of immune function used in sepsis research.
The main comparison sat at the edge of conventional statistical significance, and the authors' conclusion was cautious, saying thymosin alpha-1 "may be effective" in a targeted population. TESTS, from an overlapping group of investigators, was the larger placebo-controlled test of that idea.
The TESTS trial in detail
TESTS randomised adults with sepsis to thymosin alpha-1 or a matching placebo for up to seven days, on top of standard care. The full report, including the regimen used, is open access in PubMed Central.
| Measure | Thymosin alpha-1 | Placebo |
|---|---|---|
| Participants analysed (modified ITT) | n = 542 | n = 547 |
| All-cause mortality at 28 days | 23.4% | 24.1% |
| Hazard ratio (95% CI) | 0.99; 95% CI 0.77–1.27 | reference |
| P value | 0.93 |
No secondary outcome and no safety outcome differed between the groups.
Two prespecified subgroup analyses drew attention:
- Age. The hazard ratio was 1.67 (95% CI 1.04–2.67) in participants younger than 60 and 0.81 (95% CI 0.61–1.09) in those aged 60 or older, with an interaction P value of 0.01.
- Diabetes. The hazard ratio was 0.58 (95% CI 0.35–0.99) in participants with diabetes and 1.16 (95% CI 0.87–1.53) in those without, with an interaction P value of 0.04.
The authors described these as hypothesis-generating rather than as findings, which is the standard reading of subgroup results in a trial whose primary outcome was neutral. The trial was funded in part by SciClone Pharmaceuticals, and some authors reported grants or consultancy fees from the company. The BMJ published a correction to the paper in May 2025.
How TESTS changes the pooled evidence
A meta-analysis published in September 2025 (Gu et al., Frontiers in Cellular and Infection Microbiology) pooled 11 randomised trials. Across all trials, the odds of death were lower with thymosin alpha-1 (odds ratio 0.73). When the analysis was limited to higher-quality trials (OR 0.82, P=0.09) or multicentre trials (OR 0.86, P=0.20), the difference was no longer statistically significant. A trial sequential analysis judged that the total sample was still too small to reach a firm conclusion.
This pattern is common in research: smaller and single-centre trials tend to show larger effects, and the estimate shrinks as larger, blinded trials are added. TESTS is now the largest placebo-controlled trial in this setting, and it carries much of the weight in any pooled estimate.
Regulatory status
- United States. Thymosin alpha-1 is not an FDA-approved drug. FDA's page on bulk drug substances that may present significant safety risks lists "Thymosin-alpha 1 (Ta1)". FDA states that compounded drugs containing it may pose a significant risk of immunogenicity for certain routes of administration and may have complexities with peptide-related impurities and characterisation of the active ingredient, and that the safety information is inadequate.
- Sport. Peptides without approval by any governmental health authority fall under Category S0 of the WADA Prohibited List; see our report on the WADA Prohibited List and research peptides for how that category works.
For how to weigh a trial result against a regulatory record, see how to read a research or regulatory signal.
Limitations of the evidence
- TESTS and ETASS were both conducted in China, so the results may not carry over to other health systems or sepsis populations.
- Subgroup findings for age and diabetes come from a trial with a neutral primary outcome and need confirmation in a dedicated trial.
- ETASS was much smaller than TESTS, and its primary result sat at the edge of statistical significance.
- The meta-analysis combined trials with different designs, sizes and risk of bias.
- The trial evidence concerns the pharmaceutical peptide in hospital research settings. It says nothing about research-grade material sold for laboratory use.
Key terms
- Sepsis. Life-threatening organ dysfunction caused by a dysregulated host response to infection.
- Modified ITT (mITT). An analysis of randomised participants that excludes a small, prespecified set, such as those who never received the study drug.
- Hazard ratio. The ratio of event rates over time between two groups; 1.0 means no difference.
- Monocyte HLA-DR. A cell-surface marker measured in sepsis research as an indicator of immune suppression.
- Trial sequential analysis. A method that checks whether a meta-analysis has enough participants to support a firm conclusion.
Where researchers source it
Purita is a store that lists thymosin alpha-1 for laboratory research use only. Its product page labels the item for research use only and not for human or animal administration.
Affiliate disclosure: this is a paid link. KlowSignal earns a commission if a purchase is made through it, at no extra cost to the buyer. A listing is not an endorsement or a statement about product quality. See the affiliate disclosure.
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