[Should patients with severe sepsis be treated with activated protein C?]

Abstract

Background: Xigris (recombinant human activated protein C) has recently been introduced as a treatment for severe sepsis following a large multicentre trial (the PROWESS trial).

Material and methods: Critical review of the original paper, follow-up studies and commentaries, and subgroup analyses from the US Food and Drug Administration.

Results: Changes in trial design after the start of the trial as well as inconsistent results in two phases of the trial make interpretation difficult. The overall trial results indicate a small benefit from treatment with activated protein C. However, subgroup analysis reveals that several groups of patients appeared to have little benefit. The drug may have severe and potentially lethal side effects in some patients.

Interpretation: Although activated protein C may have beneficial effects in some patients with severe sepsis, the effect on different subgroups of patients remains to be clarified. We conclude that there is at present insufficient documentation for a recommendation of activated protein C in patients with severe sepsis.