Adverse outcomes associated with the use of drotrecogin alfa (activated) in patients with severe sepsis and baseline bleeding precautions.
BACKGROUND
Key clinical trials involving drotrecogin alfa (activated) (or recombinant human activated protein C) excluded patients with specific baseline bleeding precautions. However, not all such precautions are considered contraindications to treatment with recombinant human activated protein C in current product labeling.


OBJECTIVE
To compare outcomes of patients receiving recombinant human activated protein C with or without baseline bleeding precautions as defined by the Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) trial.


METHODS
Retrospective medical record review.


METHODS
Two tertiary care institutions: An academic medical center and an affiliated Veterans Affairs Medical Center.


METHODS
All patients receiving recombinant human activated protein C for treatment of sepsis.


METHODS
Demographic information, characteristics associated with inclusion and exclusion criteria of the PROWESS trial, and 30-day postdischarge outcomes.


RESULTS
Seventy-three patients received recombinant human activated protein C. Serious bleeding events occurred in 7 of 20 patients (35%) with any baseline bleeding precaution vs. only 2 of 53 patients (3.8%) without any bleeding precautions (p < 0.0001). More patients with a baseline bleeding precaution died compared with patients without any bleeding precautions (65% vs. 24.5%, p = 0.0015). Patients with a baseline bleeding precaution had a higher mean Acute Physiology and Chronic Health Evaluation II score (27.5 vs. 22.7, p = 0.015). Multivariate analysis demonstrated that the presence of a baseline bleeding precaution was the only independent variable associated with occurrence of serious bleeding events. The presence of a baseline bleeding precaution, increased Acute Physiology and Chronic Health Evaluation II score, and the presence of bloodstream infection were independent variables associated with mortality.


CONCLUSIONS
Patients with severe sepsis who received recombinant human activated protein C with baseline bleeding precautions as defined by product labeling had significantly higher rates of both serious bleeding events and deaths compared with those without bleeding precautions. These data suggest that strict adherence to PROWESS trial exclusion criteria would further limit serious bleeding events associated with the use of recombinant human activated protein C.
Gentry
Chris A
CA
Pharmacy Service, Department of Veterans Affairs Medical Center, Oklahoma City, OK, USA. chris.gentry@va.gov
Gross
Kristin Busse
KB
Sud
Bhanu
B
Drevets
Douglas A
DA
D000890:Anti-Infective Agents / Q000009:adverse effects*; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced* / Q000517:prevention & control*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011486:Protein C / Q000009:adverse effects*; D011994:Recombinant Proteins / Q000009:adverse effects; D012189:Retrospective Studies; D018805:Sepsis / Q000188:drug therapy*; D012720:Severity of Illness Index
D000890:Anti-Infective Agents; D011486:Protein C; D011994:Recombinant Proteins; C421124:drotrecogin alfa activated