The Reset-α Study: A Double Blind, Randomized, Multi Centre, Phase III Trial for the Efficacy and Safety of Thymosin α-1 (Tα1) in Sepsis Patients

Sameel, Samvveda S and Chaudhry, Dhruva and Jagathkar, Ganshyam M and Gupta, Amrita and Gaikwad, Vijay and Valupadas, Chandrasekhar and Satyaprasad, V and Jain, Anshul and Sree, M Usha and Srivastava, Shashank (2025) The Reset-α Study: A Double Blind, Randomized, Multi Centre, Phase III Trial for the Efficacy and Safety of Thymosin α-1 (Tα1) in Sepsis Patients. World Journal of Advanced Research and Reviews, 27 (1). pp. 931-941. ISSN 2581-9615

Aims and Background: Thymosin alpha 1 (Tα1) has shown promise as an adjuvant treatment for sepsis. This study evaluated the efficacy and safety of Tα1 versus placebo, both combined with standard care, in patients with sepsis. Methods: This was a multicenter, randomized, double-blind, placebo-controlled Phase III trial. Patients received four injections of Tα1 (2 vials twice daily) or placebo subcutaneously from Day 1 to Day 7 along with standard care. The primary endpoint was the change in Sequential Organ Failure Assessment (SOFA) score. Secondary endpoints included incidence of emerging infections, pathogen clearance rate, ICU/ventilator/vasoactive-agent-free days, changes in lymphocyte markers (CD4/CD8, NLR), TNFα , CRP, mortality, and adverse events (AEs). Results: Of 131 screened, 123 patients were enrolled across 10 sites. Mean SOFA score reduction was greater in the Tα1 arm (-3.5 ±1.7) versus placebo (-1.13 ±1.2), showing statistical significance. ICU and vasoactive-agent-free days were also significantly higher in the Tα1 arm. Both groups showed reductions in TNF, NLR, and CRP; however, only the Tα1 group showed statistically significant reductions from baseline on Day 7. Mortality was lower in the Tα1 group. Treatment-emergent AEs occurred in 48.4% of Tα1 patients and 72.1% of placebo patients, mostly mild and resolved without sequelae. Septic shock occurred in 3 (Tα1) vs. 5 (placebo) patients. Conclusion: Tα1 appears to be a safe and effective adjunct to standard care in sepsis, demonstrating significant improvements in organ dysfunction and clinical outcomes.