title: A retrospective observational study of drotrecogin alfa (activated) in adults with severe sepsis: comparison with a controlled clinical trial.
abstract: OBJECTIVE
  To compare characteristics and outcomes of patients treated with drotrecogin alfa (activated) (DrotAA) in clinical practice to those treated in a phase III randomized controlled trial (PROWESS).
  
  
  METHODS
  Observational data were collected retrospectively from patients who received DrotAA as part of physician-directed treatment.
  
  
  METHODS
  Intensive care units of five teaching institutions.
  
  
  METHODS
  Patients were > or = 18 yrs old, had severe sepsis (confirmed/suspected infection with one or more sepsis-induced organ dysfunctions), and received DrotAA.
  
  
  METHODS
  None.
  
  
  RESULTS
  Baseline demographics, severity of illness, time from organ dysfunction onset to DrotAA treatment, daily assessment of organ dysfunction, serious bleeding events, and in-hospital mortality were reported. Timing from severe sepsis documentation to start of DrotAA infusion was categorized: day 0 (same calendar day); day 1 (next calendar day); and day > or = 2 (second calendar day or later). Clinical practice patients (n = 274) were younger, had more comorbidities, had higher severity of illness (as measured by organ dysfunction or greater vasopressor/ventilator use), and received DrotAA later than PROWESS patients (all p < .05). Overall hospital mortality for clinical practice patients was 42%, compared with 37% for DrotAA-treated PROWESS patients with Acute Physiology and Chronic Health Evaluation II score > or = 25. Mortality for day 0, day 1, and day > or = 2 groups was 33%, 40%, and 52%, respectively. In PROWESS, the vast majority were treated on day 0 or day 1. Serious bleeding events during infusion were noted in 4.0% of clinical practice patients compared with 2.2% of PROWESS DrotAA-treated patients with Acute Physiology and Chronic Health Evaluation II score > or = 25.
  
  
  CONCLUSIONS
  Patients treated in clinical practice differed from those in PROWESS. Patients were younger, had more comorbidities, had greater severity of illness, and had longer mean time from severe sepsis onset to the start of DrotAA. Hospital mortality for patients treated within 1 day of severe sepsis onset was similar to DrotAA-treated PROWESS patients. While the low number of serious bleeding events precludes a definitive assessment, the observed incidence of serious bleeding events in clinical practice patients was numerically higher than in DrotAA-treated PROWESS patients.
authors.affiliation: Vanderbilt Medical Center, Nashville, TN, USA. art.wheeler@vanderbilt.edu
authors.forename: Arthur
authors.initials: A
authors.lastname: Wheeler
authors.forename: Jay
authors.initials: J
authors.lastname: Steingrub
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Schmidt
authors.forename: Philip
authors.initials: P
authors.lastname: Sanchez
authors.forename: Judith
authors.initials: J
authors.lastname: Jacobi
authors.forename: Walter
authors.initials: W
authors.lastname: Linde-Zwirble
authors.forename: Becky
authors.initials: B
authors.lastname: Bates
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Qualy
authors.forename: Brad
authors.initials: B
authors.lastname: Woodward
authors.forename: Michael
authors.initials: M
authors.lastname: Zeckel
mesh_terms: D018806:APACHE; D000328:Adult; D001741:Black or African American / Q000706:statistics & numerical data; D017677:Age Distribution; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D009202:Cardiomyopathies / Q000453:epidemiology; D017326:Clinical Trials, Phase III as Topic; D015897:Comorbidity; D005260:Female; D006470:Hemorrhage / Q000453:epidemiology; D017052:Hospital Mortality; D006801:Humans; D008107:Liver Diseases / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology; D019370:Observation; D011364:Professional Practice / Q000706:statistics & numerical data*; D011486:Protein C / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012189:Retrospective Studies; D018805:Sepsis / Q000188:drug therapy* / Q000453:epidemiology*; D014481:United States / Q000453:epidemiology
chemical_list: D000890:Anti-Infective Agents; D011486:Protein C; D011994:Recombinant Proteins; C421124:drotrecogin alfa activated