title: Drotrecogin alfa (activated) in the treatment of severe sepsis patients with multiple-organ dysfunction: data from the PROWESS trial.
abstract: OBJECTIVE
  Based on the results of the PROWESS trial the European Agency for the Evaluation of Medicinal Products has recently approved drotrecogin alfa (activated) for treatment of adult patients with severe sepsis and multiple-organ failure. We report study's data on efficacy and safety in patients with multiple-organ dysfunction.
  
  
  METHODS
  Randomized, double-blind, placebo-controlled, multicenter trial in 164 medical centers.
  
  
  METHODS
  1271 patients (75.2% of the intention-to-treat population, n=1690) with multiple-organ dysfunction at study entry.
  
  
  METHODS
  Drotrecogin alfa (activated) n=634, 24 micro g/kg per hour for 96 h or placebo ( n=637).
  
  
  RESULTS
  Observed 28-day mortality was significantly lower with drug treatment than with placebo (26.5%vs. 33.9%), cardiovascular and respiratory organ dysfunction resolved more rapidly over the first 7 days, and serious bleeding events were more frequent (2.4% vs. 1.3%).
  
  
  CONCLUSIONS
  Treatment with drotrecogin alfa (activated) significantly reduced 28-day mortality and more quickly resolved cardiovascular and respiratory organ dysfunction. The difference in serious bleeding event rates may be clinically significant; however, the overall benefit-risk profile appears favorable.
authors.affiliation: Department of Intensive Care, Cochin Hospital AP-HP, Cochin Institute, Cochin Port-Royal Medical School, Paris V University, 27 rue due Faubourg Saint Jacques, 75679, Paris cedex 14, France. jean-francois.dhainaut@cch.ap-hop-paris.fr.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Dhainaut
authors.affiliation: Department of Critical Care and Emergency Medicine, Cliniques Universitaires St. Luc, Brussels, Belgium.
authors.forename: Pierre-François
authors.initials: PF
authors.lastname: Laterre
authors.affiliation: Lilly Research Centre, Eli Lilly & Co. Ltd., Erl Wood Manor, Surrey, UK.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Janes
authors.affiliation: Divisions of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University School of Medicine, Nashville, Tenn., USA.
authors.forename: Gordon R
authors.initials: GR
authors.lastname: Bernard
authors.affiliation: Critical Care Center, Sabadell Hospital, University Institute parc Tauli, Autonomous University of Barcelona, Sabadell, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Artigas
authors.affiliation: Isala Klinieken, Zwolle, The Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: Bakker
authors.affiliation: Universitätsklinikum Charité,Medizinische Klinik für Haematologie und Onkologie, Humbolt Universität, Berlin, Germany.
authors.forename: Hanno
authors.initials: H
authors.lastname: Riess
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Ind., USA.
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Basson
authors.affiliation: Department of Intensive Care, Cochin Hospital AP-HP, Cochin Institute, Cochin Port-Royal Medical School, Paris V University, 27 rue due Faubourg Saint Jacques, 75679, Paris cedex 14, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Charpentier
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Ind., USA.
authors.forename: Barbara G
authors.initials: BG
authors.lastname: Utterback
authors.affiliation: Department of Intensive Care, Erasme University Hospital, Free University of Brussels, Brussels, Belgium.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Vincent
mesh_terms: D018806:APACHE; D000368:Aged; D000890:Anti-Infective Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D004311:Double-Blind Method; D005060:Europe / Q000453:epidemiology; D005260:Female; D005343:Fibrinolytic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000175:diagnosis / Q000382:microbiology* / Q000401:mortality; D016016:Proportional Hazards Models; D011486:Protein C / Q000009:adverse effects / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use*; D012307:Risk Factors; D018805:Sepsis / Q000150:complications* / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism; D016019:Survival Analysis; D013927:Thrombosis / Q000139:chemically induced; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology
chemical_list: D000890:Anti-Infective Agents; D015415:Biomarkers; D005343:Fibrinolytic Agents; D011486:Protein C; D011994:Recombinant Proteins; C421124:drotrecogin alfa activated