title: The efficacy of thymosin alpha 1 for severe sepsis (ETASS): a multicenter, single-blind, randomized and controlled trial.
abstract: BACKGROUND
  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.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00711620.
authors: Jianfeng
authors: J
authors: Wu
authors: Lixin
authors: L
authors: Zhou
authors: Jiyun
authors: J
authors: Liu
authors: Gang
authors: G
authors: Ma
authors: Qiuye
authors: Q
authors: Kou
authors: Zhijie
authors: Z
authors: He
authors: Juan
authors: J
authors: Chen
authors: Bin
authors: B
authors: Ou-Yang
authors: Minying
authors: M
authors: Chen
authors: Yinan
authors: Y
authors: Li
authors: Xiaoqin
authors: X
authors: Wu
authors: Baochun
authors: B
authors: Gu
authors: Lei
authors: L
authors: Chen
authors: Zijun
authors: Z
authors: Zou
authors: Xinhua
authors: X
authors: Qiang
authors: Yuanyuan
authors: Y
authors: Chen
authors: Aihua
authors: A
authors: Lin
authors: Guanrong
authors: G
authors: Zhang
authors: Xiangdong
authors: X
authors: Guan
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D018805:Sepsis / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality*; D016037:Single-Blind Method; D015996:Survival Rate / Q000639:trends; D000077596:Thymalfasin; D013947:Thymosin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016896:Treatment Outcome
chemical_list: D000276:Adjuvants, Immunologic; D013947:Thymosin; D000077596:Thymalfasin