Thymosin Alpha-1 Tested to Prevent Organ Failure After Emergency Aortic Surgery

Acute type A aortic dissection (ATAAD) is one of the most catastrophic cardiovascular emergencies, carrying perioperative mortality rates exceeding 20–30% even at experienced centers. Survivors of emergency surgical repair face a second major threat: a profound systemic inflammatory response syndrome (SIRS) triggered by the combination of the dissection itself, prolonged cardiopulmonary bypass, deep hypothermic circulatory arrest, and ischemia-reperfusion injury. This inflammatory cascade drives multi-organ dysfunction affecting the heart, lungs, kidneys, brain, and liver, and is a leading cause of postoperative death and prolonged ICU stays. Despite advances in surgical technique, no pharmacological intervention has been proven to reliably attenuate this immune-mediated organ injury.

Thymosin alpha-1 (Tα1) is a 28-amino-acid peptide originally isolated from thymic tissue that plays a central role in regulating both innate and adaptive immunity. It promotes T-cell maturation and differentiation, enhances natural killer cell activity, modulates dendritic cell function, and suppresses excessive pro-inflammatory cytokine release — making it a mechanistically attractive candidate for the post-ATAAD immune imbalance state. Tα1 is already approved in China and several other countries for use in chronic hepatitis B, hepatitis C, and as an adjunct in cancer immunotherapy. Its safety profile is well established, and a predecessor pilot study (PANDA I) provided preliminary evidence of benefit in the ATAAD surgical context, justifying this larger confirmatory trial.

The PANDA II trial is a multicenter, double-blind, placebo-controlled randomized controlled trial registered at ClinicalTrials.gov (NCT05339529). A total of 330 patients undergoing emergency ATAAD repair will be enrolled across 17 cardiovascular surgery centers in China and randomized 1:1 to receive either Tα1 (1.6 mg subcutaneously) plus standard perioperative care or matching placebo plus standard care. The intervention begins perioperatively and continues through the early postoperative period. The primary endpoint is the mean Sequential Organ Failure Assessment (SOFA) score calculated daily from postoperative days 1 through 7, with the between-group difference in mean SOFA score serving as the key efficacy measure. SOFA is a validated, composite tool scoring dysfunction across six organ systems (respiratory, coagulation, hepatic, cardiovascular, neurological, and renal), making it well suited to capture the breadth of post-ATAAD organ injury.

Secondary endpoints are comprehensive and clinically meaningful. They include all-cause mortality at 30 days and 6 months, incidence of specific organ complications (acute kidney injury, respiratory failure, neurological events, hepatic dysfunction), duration of mechanical ventilation, ICU length of stay, total hospital stay, and serial measurements of inflammatory biomarkers including interleukin-6, tumor necrosis factor-alpha, and lymphocyte subset counts. These secondary endpoints will help characterize both the mechanism of any observed benefit and its durability beyond the acute hospitalization period. The 6-month follow-up window is particularly important given that immune dysregulation after major cardiac surgery can persist for weeks to months.

The trial is powered to detect a clinically meaningful reduction in mean SOFA score with 80% power at a two-sided alpha of 0.05, with 330 patients providing adequate statistical power after accounting for expected dropout. The multicenter design across 17 institutions spanning multiple Chinese provinces strengthens external validity and enrollment feasibility. As a protocol paper, no efficacy results are yet available. Key limitations include the single-country design, which may limit generalizability to non-Chinese populations with different baseline characteristics and surgical practices. The trial also relies on SOFA as a surrogate endpoint rather than mortality alone, though SOFA is strongly predictive of outcomes in this population. If positive, PANDA II could establish Tα1 as the first proven immunomodulatory adjunct for ATAAD surgery — a significant advance for a condition where surgical technique has plateaued but immune-mediated complications remain a major unmet need.