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.