title: International integrated database for the evaluation of severe sepsis and drotrecogin alfa (activated) therapy: 28-day survival and safety.
abstract: 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.
authors.affiliation: Department of Critical Care Medicine, Hôpital St Luc, Université Catholique de Louvain, B-1200 Brussels, Belgium. laterre@rean.ucl.ac.be
authors.forename: Pierre-Francois
authors.initials: PF
authors.lastname: Laterre
authors.forename: David R
authors.initials: DR
authors.lastname: Nelson
authors.forename: William
authors.initials: W
authors.lastname: Macias
authors.forename: Edward
authors.initials: E
authors.lastname: Abraham
authors.forename: Andreas
authors.initials: A
authors.lastname: Sashegyi
authors.forename: Mark D
authors.initials: MD
authors.lastname: Williams
authors.forename: Mitchell
authors.initials: M
authors.lastname: Levy
authors.forename: Marcel
authors.initials: M
authors.lastname: Levi
authors.forename: Barbara
authors.initials: B
authors.lastname: Utterback
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Vincent
mesh_terms: 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
chemical_list: D000890:Anti-Infective Agents; D011486:Protein C; D011994:Recombinant Proteins; C421124:drotrecogin alfa activated