Drotrecogin alfa (activated) in the treatment of severe sepsis patients with multiple-organ dysfunction: data from the PROWESS trial.
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.
Dhainaut
Jean-François
JF
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.
Laterre
Pierre-François
PF
Department of Critical Care and Emergency Medicine, Cliniques Universitaires St. Luc, Brussels, Belgium.
Janes
Jonathan M
JM
Lilly Research Centre, Eli Lilly & Co. Ltd., Erl Wood Manor, Surrey, UK.
Bernard
Gordon R
GR
Divisions of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University School of Medicine, Nashville, Tenn., USA.
Artigas
Antonio
A
Critical Care Center, Sabadell Hospital, University Institute parc Tauli, Autonomous University of Barcelona, Sabadell, Spain.
Bakker
Jan
J
Isala Klinieken, Zwolle, The Netherlands.
Riess
Hanno
H
Universitätsklinikum Charité,Medizinische Klinik für Haematologie und Onkologie, Humbolt Universität, Berlin, Germany.
Basson
Bruce R
BR
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Ind., USA.
Charpentier
Julien
J
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.
Utterback
Barbara G
BG
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Ind., USA.
Vincent
Jean-Louis
JL
Department of Intensive Care, Erasme University Hospital, Free University of Brussels, Brussels, Belgium.
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
D000890:Anti-Infective Agents; D015415:Biomarkers; D005343:Fibrinolytic Agents; D011486:Protein C; D011994:Recombinant Proteins; C421124:drotrecogin alfa activated