Hospital mortality and resource use in subgroups of the Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) trial *

Abstract

To compare differences in hospital mortality and resource use in adult severe sepsis subjects randomized to receive drotrecogin alfa (activated) (DrotAA) or placebo in the PROWESS trial. Retrospective, cross-sectional, blinded follow-up of subjects enrolled in a previous randomized, controlled trial. One hundred sixty-four tertiary care institutions in 11 countries. The 1,690 subjects with severe sepsis enrolled and treated with study drug in PROWESS, of whom 1,220 were alive at 28 days (the end of the original PROWESS follow-up). DrotAA (n = 850), 24 microg/kg/hr for 96 hrs, or placebo (n = 840). New follow-up data through hospital discharge were merged with existing 28-day follow-up data. Hospital mortality was calculated for designated subgroups. Intensive care unit and hospital length of stay and Simplified Therapeutic Intervention Scoring System-28 (TISS-28) scores were calculated overall and in designated subgroups. Hospital discharge location was recorded. The 95% confidence interval of most subgroups contained the relative risk estimate for overall 28-day and hospital mortality. Median hospital length of stay and intensive care unit length of stay were similar in both treatment groups: 16 vs. 17 days (p = .22) and 9 vs. 9 days (p = .7) for placebo vs. DrotAA. No significant difference in TISS-28 scores was observed between treatment groups overall or in subgroups of disease severity. In subjects for whom discharge destination was reported, 42.8% of placebo subjects and 46.8% of DrotAA subjects (two thirds of survivors in each group) were discharged directly to home. Reduction in hospital mortality with DrotAA in most of the subgroups of PROWESS is consistent with the reduction in 28-day and hospital mortality observed in the overall PROWESS population. Additional survivors created with DrotAA treatment did not increase per-patient resource use or intensive care unit or hospital length of stay.