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

Abstract

INTRODUCTION:

Severe sepsis is associated with a high mortality rate despite implementation of guideline recommendations. Adjunctive treatment may be efficient and require further investigation. In light of the crucial role of immunologic derangement in severe sepsis, thymosin alpha 1 (Tα1) is considered as a promising beneficial immunomodulatory drug. The trial is to evaluate whether Tα1 improves 28-day all-cause mortality rates and immunofunction in patients with severe sepsis.

METHODS:

We performed a multicenter randomized controlled trial in six tertiary, teaching hospitals in China between May 12, 2008 and Dec 22, 2010. Eligible patients admitted in ICU with severe sepsis were randomly allocated by a central randomization center to the control group or Tα1 group (1:1 ratio). The primary outcome was death from any cause and was assessed 28 days after enrollment. Secondary outcomes included dynamic changes of Sequential Organ Failure Assessment (SOFA) and monocyte human leukocyte antigen-DR (mHLA-DR) on day 0, 3, 7 in both groups. All analyses were done on an intention-to-treat basis.

RESULTS:

A total of 361 patients were allocated to either the control group (n = 180) or Tα1 (n = 181) group. The mortalities from any cause within 28 days in the Tα1 group and control group were 26.0% and 35.0% respectively with a marginal P value (nonstratified analysis, P = 0.062; log rank, P = 0.049); the relative risk of death in the Tα1 group as compared to the control group was 0.74 (95% CI 0.54 to 1.02). Greater improvement of mHLA-DR was observed in the Tα1 group on day 3 (mean difference in mHLA-DR changes between the two groups was 3.9%, 95% CI 0.2 to 7.6%, P = 0.037) and day 7 (mean difference in mHLA-DR changes between the two groups was 5.8%, 95% CI 1.0 to 10.5%, P = 0.017) than in the control group. No serious drug-related adverse event was recorded.

CONCLUSIONS:

The use of Tα1 therapy in combination with conventional medical therapies may be effective in improving clinical outcomes in a targeted population of severe sepsis.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00711620.

• Authors: Jianfeng Wu, Lixin Zhou, Jiyun Liu, Gang Ma, Qiuye Kou, Zhijie He, Juan Chen, Bin Ou-Yang, Minying Chen, Yinan Li, Xiaoqin Wu, Baochun Gu, Lei Chen, Zijun Zou, Xinhua Qiang, Yuanyuan Chen, Aihua Lin, Guanrong Zhang, Xiangdong Guan
• Journal: Critical care (London, England) (Crit Care) Vol. 17 Issue 1 Pg. R8 (Jan 17 2013) ISSN: 1466-609X [Electronic] England
• PMID: 23327199 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Adjuvants, Immunologic
• Thymosin
• Thymalfasin

Topics

• Adjuvants, Immunologic (administration & dosage)
• Aged
• Aged, 80 and over
• Female
• Humans
• Injections, Subcutaneous
• Male
• Middle Aged
• Prospective Studies
• Sepsis (diagnosis, drug therapy, mortality)
• Single-Blind Method
• Survival Rate (trends)
• Thymalfasin
• Thymosin (administration & dosage, analogs & derivatives)
• Treatment Outcome