International integrated database for the evaluation of severe sepsis and drotrecogin alfa (activated) therapy: 28-day survival and safety

PurposeTo enhance the understanding of severe sepsis, a database of patients from multiple clinical trials spanning a 6-year period was constructed. Initial analyses evaluated the 28-day survival in the placebo group and further assessed the treatment effect of drotrecogin alfa (activated) (DrotAA).MethodsFive severe sepsis studies with similar entry criteria were combined, and baseline characteristics and 28-day mortality were evaluated (4459 severe sepsis patients; placebo, n = 1231; DrotAA, n = 3228). An integrated data analysis with propensity score adjustment was performed. Twenty-one variables selected by stepwise logistic regression were included in a propensity score of differences between the 2 groups of patients.ResultsOver the 6-year period of these trials, there was no change in placebo mortality rates overall (P = .67), nor in subgroups of Acute Physiology and Chronic Health Evaluation score ≥25 (P = .73) or multiple organ dysfunction (P = .38). The adjusted relative hazard risk for DrotAA patients was 0.84 (95% confidence interval, 0.73-0.95; P = .007). Serious bleeding (0.8% in placebo vs 3.5% in DrotAA, P < .0001) was increased during the DrotAA infusion period.ConclusionsInitial analyses indicate that placebo mortality remained unchanged over a recent 6-year period. These analyses also further substantiate that treatment with DrotAA is associated with improved survival.