Hospital mortality and resource use in subgroups of the Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) trial.
OBJECTIVE
To compare differences in hospital mortality and resource use in adult severe sepsis subjects randomized to receive drotrecogin alfa (activated) (DrotAA) or placebo in the PROWESS trial.


METHODS
Retrospective, cross-sectional, blinded follow-up of subjects enrolled in a previous randomized, controlled trial.


METHODS
One hundred sixty-four tertiary care institutions in 11 countries.


METHODS
The 1,690 subjects with severe sepsis enrolled and treated with study drug in PROWESS, of whom 1,220 were alive at 28 days (the end of the original PROWESS follow-up).


METHODS
DrotAA (n = 850), 24 microg/kg/hr for 96 hrs, or placebo (n = 840).


RESULTS
New follow-up data through hospital discharge were merged with existing 28-day follow-up data. Hospital mortality was calculated for designated subgroups. Intensive care unit and hospital length of stay and Simplified Therapeutic Intervention Scoring System-28 (TISS-28) scores were calculated overall and in designated subgroups. Hospital discharge location was recorded. The 95% confidence interval of most subgroups contained the relative risk estimate for overall 28-day and hospital mortality. Median hospital length of stay and intensive care unit length of stay were similar in both treatment groups: 16 vs. 17 days (p = .22) and 9 vs. 9 days (p = .7) for placebo vs. DrotAA. No significant difference in TISS-28 scores was observed between treatment groups overall or in subgroups of disease severity. In subjects for whom discharge destination was reported, 42.8% of placebo subjects and 46.8% of DrotAA subjects (two thirds of survivors in each group) were discharged directly to home.


CONCLUSIONS
Reduction in hospital mortality with DrotAA in most of the subgroups of PROWESS is consistent with the reduction in 28-day and hospital mortality observed in the overall PROWESS population. Additional survivors created with DrotAA treatment did not increase per-patient resource use or intensive care unit or hospital length of stay.
Laterre
Pierre-Francois
PF
Department of Critical Care, St Luc University Hospital, UCL, Brussels, Belgium.
Levy
Howard
H
Clermont
Gilles
G
Ball
Daniel E
DE
Garg
Rekha
R
Nelson
David R
DR
Dhainaut
Jean-Francois
JF
Angus
Derek C
DC
D018806:APACHE; D000203:Activities of Daily Living; D000368:Aged; D000890:Anti-Infective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001424:Bacterial Infections / Q000150:complications / Q000188:drug therapy / Q000401:mortality; D003430:Cross-Sectional Studies; D005260:Female; D005500:Follow-Up Studies; D006295:Health Resources / Q000706:statistics & numerical data*; D017052:Hospital Mortality; D006801:Humans; D007262:Infusions, Intravenous; D007362:Intensive Care Units / Q000706:statistics & numerical data; D007902:Length of Stay / Q000706:statistics & numerical data; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000382:microbiology; D010351:Patient Discharge / Q000706:statistics & numerical data; D018579:Patient Selection; D011486:Protein C / Q000494:pharmacology / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D012189:Retrospective Studies; D012307:Risk Factors; D018805:Sepsis / Q000150:complications / Q000188:drug therapy* / Q000401:mortality*; D016019:Survival Analysis; D016896:Treatment Outcome
D000890:Anti-Infective Agents; D011486:Protein C; D011994:Recombinant Proteins; C421124:drotrecogin alfa activated