TY - JOUR
T1 - International integrated database for the evaluation of severe sepsis and drotrecogin alfa (activated) therapy: 28-day survival and safety
AU - Laterre, Pierre-Francois
AU - Nelson, David R.
AU - Macias, William
AU - Abraham, Edward
AU - Sashegyi, Andreas
AU - Williams, Mark D.
AU - Levy, Mitchell
AU - Levi, Marcel
AU - Utterback, Barbara
AU - Vincent, Jean-Louis
PY - 2007
Y1 - 2007
N2 - 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
AB - 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
U2 - https://doi.org/10.1016/j.jcrc.2006.09.007
DO - https://doi.org/10.1016/j.jcrc.2006.09.007
M3 - Article
C2 - 17548026
SN - 0883-9441
VL - 22
SP - 142
EP - 152
JO - Journal of Critical Care
JF - Journal of Critical Care
IS - 2
ER -