Activated protein C: do more survive?

Excerpt

Severe sepsis kills [1]—hence the enthusiasm that greeted publication of the Recombinant Human Activated Protein C (APC) Worldwide Evaluation in Severe Sepsis (PROWESS) trial [2], the first adequately powered randomised controlled trial in severe sepsis to show a statistically significant reduction in 28-day mortality (APC 210/850=25%, placebo 259/840=31%). However, enthusiasm was not universal. The 20-person Anti-infective Drug Advisory Committee to the United States Food and Drug Administration (FDA), after examining unpublished PROWESS data [3], was divided 10:10 on whether efficacy and safety had actually been demonstrated [4]. As subgroup data suggested greater effect in groups with higher Acute Physiology and Chronic Health Evaluation (APACHE II; >24), the FDA eventually granted limited approval for APC use in “adult patients with severe sepsis and a high risk of death (e.g. as determined by APACHE II)”, on condition that further studies were performed [4]. Information from these studies has recently emerged [5, 6, 7]. …