title: Drotrecogin alfa (activated) in adults with septic shock.
abstract: BACKGROUND
  There have been conflicting reports on the efficacy of recombinant human activated protein C, or drotrecogin alfa (activated) (DrotAA), for the treatment of patients with septic shock.
  
  
  METHODS
  In this randomized, double-blind, placebo-controlled, multicenter trial, we assigned 1697 patients with infection, systemic inflammation, and shock who were receiving fluids and vasopressors above a threshold dose for 4 hours to receive either DrotAA (at a dose of 24 μg per kilogram of body weight per hour) or placebo for 96 hours. The primary outcome was death from any cause 28 days after randomization.
  
  
  RESULTS
  At 28 days, 223 of 846 patients (26.4%) in the DrotAA group and 202 of 834 (24.2%) in the placebo group had died (relative risk in the DrotAA group, 1.09; 95% confidence interval [CI], 0.92 to 1.28; P=0.31). At 90 days, 287 of 842 patients (34.1%) in the DrotAA group and 269 of 822 (32.7%) in the placebo group had died (relative risk, 1.04; 95% CI, 0.90 to 1.19; P=0.56). Among patients with severe protein C deficiency at baseline, 98 of 342 (28.7%) in the DrotAA group had died at 28 days, as compared with 102 of 331 (30.8%) in the placebo group (risk ratio, 0.93; 95% CI, 0.74 to 1.17; P=0.54). Similarly, rates of death at 28 and 90 days were not significantly different in other predefined subgroups, including patients at increased risk for death. Serious bleeding during the treatment period occurred in 10 patients in the DrotAA group and 8 in the placebo group (P=0.81).
  
  
  CONCLUSIONS
  DrotAA did not significantly reduce mortality at 28 or 90 days, as compared with placebo, in patients with septic shock. (Funded by Eli Lilly; PROWESS-SHOCK ClinicalTrials.gov number, NCT00604214.).
authors.affiliation: Ospedale S. Giovanni Battista-Molinette, Università di Torino, Turin, Italy.
authors.forename: V Marco
authors.initials: VM
authors.lastname: Ranieri
authors.forename: B Taylor
authors.initials: BT
authors.lastname: Thompson
authors.forename: Philip S
authors.initials: PS
authors.lastname: Barie
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Dhainaut
authors.forename: Ivor S
authors.initials: IS
authors.lastname: Douglas
authors.forename: Simon
authors.initials: S
authors.lastname: Finfer
authors.forename: Bengt
authors.initials: B
authors.lastname: Gårdlund
authors.forename: John C
authors.initials: JC
authors.lastname: Marshall
authors.forename: Andrew
authors.initials: A
authors.lastname: Rhodes
authors.forename: Antonio
authors.initials: A
authors.lastname: Artigas
authors.forename: Didier
authors.initials: D
authors.lastname: Payen
authors.forename: Jyrki
authors.initials: J
authors.lastname: Tenhunen
authors.forename: Hussein R
authors.initials: HR
authors.lastname: Al-Khalidi
authors.forename: Vivian
authors.initials: V
authors.lastname: Thompson
authors.forename: Jonathan
authors.initials: J
authors.lastname: Janes
authors.forename: William L
authors.initials: WL
authors.lastname: Macias
authors.forename: Burkhard
authors.initials: B
authors.lastname: Vangerow
authors.forename: Mark D
authors.initials: MD
authors.lastname: Williams
mesh_terms: D000328:Adult; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D006801:Humans; D053208:Kaplan-Meier Estimate; D016017:Odds Ratio; D011486:Protein C / Q000627:therapeutic use*; D020151:Protein C Deficiency / Q000150:complications / Q000401:mortality; D011994:Recombinant Proteins / Q000627:therapeutic use; D012772:Shock, Septic / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D017211:Treatment Failure
chemical_list: D000890:Anti-Infective Agents; D011486:Protein C; D011994:Recombinant Proteins; C421124:drotrecogin alfa activated