title: Effects of drotrecogin alfa (activated) on organ dysfunction in the PROWESS trial.
abstract: OBJECTIVE
  To assess morbidity in patients with severe sepsis managed with and without drotrecogin alfa (activated).
  
  
  METHODS
  Analysis of secondary end points in a prospective, randomized, double-blind, placebo-controlled, multicenter, phase 3 trial (PROWESS).
  
  
  METHODS
  A total of 164 medical institutions in 11 countries.
  
  
  METHODS
  A total of 1,690 consecutive adult patients with severe sepsis.
  
  
  METHODS
  A 96-hr infusion of drotrecogin alfa (activated) (human recombinant activated protein C) or placebo.
  
  
  RESULTS
  Sequential Organ Failure Assessment (SOFA) scores for cardiovascular, respiratory, renal, hematologic, and hepatic organ systems were measured for 28 days. Mean cardiovascular SOFA scores were significantly lower for patients treated with drotrecogin alfa (activated) compared with placebo patients over this time period (p = .022). Drotrecogin alfa (activated)-treated patients also showed significantly faster resolution of cardiovascular (p = .009) and respiratory (p = .009) dysfunction and significantly slower onset of hematologic organ dysfunction (p = .041) compared with placebo patients for days 1 to 7. No significant differences in morbidity were observed between treatment groups among 28-day survivors.
  
  
  CONCLUSIONS
  Drotrecogin alfa (activated) demonstrated significant improvements in organ function compared with placebo in a large phase 3 clinical trial that has shown a mortality benefit in patients with severe sepsis.
authors.affiliation: Department of Intensive Care, Erasme University Hospital, Free University of Brussels, Belgium. jlvincen@ulb.ac.be
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Vincent
authors.forename: Derek C
authors.initials: DC
authors.lastname: Angus
authors.forename: Antonio
authors.initials: A
authors.lastname: Artigas
authors.forename: Andre
authors.initials: A
authors.lastname: Kalil
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Basson
authors.forename: Hassan H
authors.initials: HH
authors.lastname: Jamal
authors.forename: Gerald
authors.initials: G
authors.lastname: Johnson
authors.forename: Gordon R
authors.initials: GR
authors.lastname: Bernard
mesh_terms: D018806:APACHE; D000368:Aged; D000890:Anti-Infective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002423:Cause of Death; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009017:Morbidity; D009102:Multiple Organ Failure / Q000145:classification / Q000382:microbiology* / Q000401:mortality / Q000517:prevention & control*; D011446:Prospective Studies; D011486:Protein C / Q000494:pharmacology / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D012720:Severity of Illness Index; D016019:Survival Analysis; D018746:Systemic Inflammatory Response Syndrome / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000890:Anti-Infective Agents; D011486:Protein C; D011994:Recombinant Proteins; C421124:drotrecogin alfa activated