The efficacy of thymosin alpha 1 for severe sepsis (ETASS) - a multicenter, single-blind, randomized and controlled trial

Multicenter trial (ETASS) conducted in six tertiary hospitals in China between 2008 and 2010, evaluating thymosin alpha-1 (Tα1) as adjuvant therapy to standard treatment of severe sepsis in ICU. The context is mechanically important: sepsis patients develop immune paralysis (drop in mHLA-DR expression on monocytes), and Tα1 is proposed as a restorer of adaptive immune function in this scenario.

A total of 361 patients with severe sepsis were randomized 1:1 to receive Tα1 (1.6 mg subcutaneous every 12h for 5 days, then daily for 2 more days) added to standard care, or standard care alone. The primary outcome was 28-day all-cause mortality; secondary outcomes included dynamic change of SOFA score and monocytic HLA-DR (mHLA-DR) expression, a marker of immune function.

At 28 days, 47 of 181 patients in the Tα1 group (26.0%) died, versus 63 of 180 (35.0%) in the control group — an absolute reduction of 9 percentage points. The difference did not reach statistical significance on the primary outcome, but the trend was consistent across all subgroups (age, sex, APACHE II, SOFA, baseline mHLA-DR). The secondary immunologic markers showed significant improvement: mHLA-DR rose faster on days 3 and 7 in the Tα1 group, confirming the biological effect of restoring monocyte function/antigen presentation. There were no serious adverse events attributable to Tα1.

ETASS is frequently cited in meta-analyses and immunotherapy guidelines for sepsis and generated renewed interest in Tα1 for this indication. The TESTS trial (phase 3, multicenter) was subsequently designed to definitively answer the mortality question, with results published in 2025. ETASS remains the key work that established biological plausibility and the preliminary clinical signal for the use of Zadaxin in critical care medicine.