Recombinant human activated protein C for use in severe sepsis.
OBJECTIVE
To review the efficacy and safety of drotrecogin alfa (recombinant human activated protein C) in the treatment of sepsis.


METHODS
Literature was identified through a MEDLINE search (1966-January 2002), the product manufacturer, and the Food and Drug Administration.


METHODS
All relevant information identified from the data sources was evaluated.


RESULTS
Drotrecogin alfa reduces coagulation and inflammation in septic patients. A large placebo-controlled clinical trial (n = 1690) of drotrecogin alfa in severely septic patients demonstrated a reduction in mortality (24.7% vs. 30.8%; p = 0.005), with increased bleeding risks (24.9% vs. 17.7%; p <0.001). Patients with more severe sepsis appeared to gain the most benefit. The complete clinical and economic impact of this agent requires further analysis.


CONCLUSIONS
Drotrecogin alfa offers a significant advance in the treatment of severe sepsis. Judicious use in appropriate patients is necessary to control cost and maximize clinical benefits.
Bearden
David T
DT
Department of Pharmacy Practice, College of Pharmacy, Oregon State University, Portland, OR 97239-3098, USA. beardend@ohsu.edu
Garvin
Cory G
CG
D002986:Clinical Trials as Topic; D006801:Humans; D011493:Protein Kinase C / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D018805:Sepsis / Q000188:drug therapy*
D011994:Recombinant Proteins; D011493:Protein Kinase C