A prospective, observational study of Xigris Use in the United States (XEUS).
BACKGROUND
Use of pharmacologic agents in clinical practice may differ from the manner in which they were studied in rigorous randomized clinical trials. This was a prospective, observational, noninterventional study to determine the profile of patients receiving drotrecogin alfa (activated) in clinical practice, provide additional outcome and safety data, and allow for a comparison to patients studied in the phase 3 Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) trial.


METHODS
A total of 548 adult patients with severe sepsis were enrolled from 61 nonteaching or academically affiliated hospitals in the United States. Patients received drotrecogin alfa (activated) as part of physician-directed therapy for severe sepsis.


RESULTS
The Xigris Use in the United States (XEUS) patients were younger (58 vs 63 years of age), had more comorbidities, and more sepsis-induced organ dysfunction at baseline compared to high-risk (Acute Physiology and Chronic Health Evaluation II score ≥ 25) PROWESS patients who received drotrecogin alfa (activated), (cardiovascular, 85.0% vs 79.7%; hematologic, 22.3% vs 16.4%; and renal, 57.9% vs 50.7%) (all P < .05). The XEUS patients had a higher mortality rate compared to high-risk PROWESS patients receiving drotrecogin alfa (activated) (36.7% vs 30.9%; P = .062) but a similar safety profile (infusion period serious bleeding, 2.7% vs 2.2%; P = .579; 28-day serious bleeding, 3.1% vs 3.9%; P = .520). The rate of intracranial hemorrhage in XEUS was 0.2%.


CONCLUSIONS
Patients receiving drotrecogin alfa (activated) in clinical practice were more acutely ill, had a higher mortality rate, but a similar safety profile with respect to serious bleeding events compared to the PROWESS trial.
Steingrub
Jay S
JS
Division of Critical Care Medicine, Baystate Medical Center, Springfield, MA 01199, USA. jay.steingrub@baystatehealth.org
Cheatham
Michael L
ML
Woodward
Brad
B
Wang
H Tiffany
HT
Effron
Mark B
MB
D000328:Adult; D000367:Age Factors; D000368:Aged; D000890:Anti-Infective Agents / Q000009:adverse effects / Q000627:therapeutic use*; D017326:Clinical Trials, Phase III as Topic; D015897:Comorbidity; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000209:etiology; D010818:Practice Patterns, Physicians'; D011446:Prospective Studies; 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 / Q000188:drug therapy* / Q000401:mortality; D016896:Treatment Outcome; D014481:United States
D000890:Anti-Infective Agents; D011486:Protein C; D011994:Recombinant Proteins; C421124:drotrecogin alfa activated