tifacogin and Shock--Septic

Whereas antithrombin and tifacogin failed to improve clinical outcome in cases of severe sepsis, drotrecogin alfa (activated) increased the chances of survival of patients with this condition. Concerns about efficacy and safety of drotrecogin alfa have been raised because of internal and external validity and internal consistency problems found in the PROWESS study, and because of the drug's single positive pivotal phase III documentation that led to restricted marketing authorisations for only a subgroup of studied patients whose randomisation had not been stratified. Concerns intensified with data from ADDRESS, the PROWESS follow-up, and paediatric studies. It is difficult to make rational and safe recommendations for drotrecogin alfa use on the available evidence. Further trials have been suggested. The relevant bodies should review product approval in light of their own guidelines for marketing authorisations on the basis of single pivotal trials and request the further study required to prevent the possibility of patients receiving a non-efficacious and potentially lethal drug.

Topics: Adult; Anti-Infective Agents; Antithrombins; Child; Clinical Trials, Phase III as Topic; Fibrinolytic Agents; Humans; Protein C; Proteins; Randomized Controlled Trials as Topic; Recombinant Proteins; Research Design; Shock, Septic; Survival Analysis; Systemic Inflammatory Response Syndrome; Treatment Outcome