[Antithrombin therapy of no value in sepsis according to a large clinical trial]

Abstract

Antithrombin has been used for over two decades as adjuvant therapy in severe sepsis, especially when associated with coagulopathy. A positive effect has been demonstrated in several experimental sepsis models and a number of small clinical trials have suggested a beneficial effect. A large confirmatory randomized clinical trial with 2,314 evaluable patients with severe sepsis was recently completed [1]. No treatment effect of antithrombin was demonstrated (28 day overall mortality was 38.9% and 38.7% in the treatment and placebo groups, respectively). Among various secondary effect and subgroup analyses, it is noteworthy that no trend indicating a beneficial effect of antithrombin substitution was found even in the subgroup of patients with plasma levels of antithrombin < 60% on randomization (n = 1,117). In summary, there is presently no support for the general use of antithrombin as adjuvant therapy in severe sepsis/septic shock.