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

Pierre-Francois Laterre, David R. Nelson, William Macias, Edward Abraham, Andreas Sashegyi, Mark D. Williams, Mitchell Levy, Marcel Levi, Barbara Utterback, Jean-Louis Vincent

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13 Citations (Scopus)

Abstract

Purpose: To 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). Methods: Five 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. Results: Over 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. Conclusions: Initial 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. (C) 2007 Elsevier Inc. All rights reserved
Original languageEnglish
Pages (from-to)142-152
JournalJournal of critical care
Volume22
Issue number2
DOIs
Publication statusPublished - 2007

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