Effects of drotrecogin alfa (activated) on organ dysfunction in the PROWESS trial.
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.
Vincent
Jean-Louis
JL
Department of Intensive Care, Erasme University Hospital, Free University of Brussels, Belgium. jlvincen@ulb.ac.be
Angus
Derek C
DC
Artigas
Antonio
A
Kalil
Andre
A
Basson
Bruce R
BR
Jamal
Hassan H
HH
Johnson
Gerald
G
Bernard
Gordon R
GR
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
D000890:Anti-Infective Agents; D011486:Protein C; D011994:Recombinant Proteins; C421124:drotrecogin alfa activated