International integrated database for the evaluation of severe sepsis and drotrecogin alfa (activated) therapy: 28-day survival and safety.
OBJECTIVE
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.
Laterre
Pierre-Francois
PF
Department of Critical Care Medicine, Hôpital St Luc, Université Catholique de Louvain, B-1200 Brussels, Belgium. laterre@rean.ucl.ac.be
Nelson
David R
DR
Macias
William
W
Abraham
Edward
E
Sashegyi
Andreas
A
Williams
Mark D
MD
Levy
Mitchell
M
Levi
Marcel
M
Utterback
Barbara
B
Vincent
Jean-Louis
JL
D018806:APACHE; D000890:Anti-Infective Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016208:Databases, Factual / Q000706:statistics & numerical data*; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000188:drug therapy / Q000401:mortality; D016016:Proportional Hazards Models; D011486:Protein C / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D018805:Sepsis / Q000188:drug therapy* / Q000401:mortality; D015996:Survival Rate
D000890:Anti-Infective Agents; D011486:Protein C; D011994:Recombinant Proteins; C421124:drotrecogin alfa activated