title: A prospective, observational study of Xigris Use in the United States (XEUS).
abstract: 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.
authors.affiliation: Division of Critical Care Medicine, Baystate Medical Center, Springfield, MA 01199, USA. jay.steingrub@baystatehealth.org
authors.forename: Jay S
authors.initials: JS
authors.lastname: Steingrub
authors.forename: Michael L
authors.initials: ML
authors.lastname: Cheatham
authors.forename: Brad
authors.initials: B
authors.lastname: Woodward
authors.forename: H Tiffany
authors.initials: HT
authors.lastname: Wang
authors.forename: Mark B
authors.initials: MB
authors.lastname: Effron
mesh_terms: 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
chemical_list: D000890:Anti-Infective Agents; D011486:Protein C; D011994:Recombinant Proteins; C421124:drotrecogin alfa activated