title: Identifying patients with severe sepsis who should not be treated with drotrecogin alfa (activated).
abstract: Historically, clinical trials evaluating treatment of patients with severe sepsis have failed to show a reduction of mortality. However, retrospective analyses of some of these trials showed benefits in certain patient subgroups. Conversely, the recent Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) trial, which evaluated the safety and efficacy of drotrecogin alfa (activated) (Xigris; Eli Lilly and Company, Indianapolis, IN), a recombinant form of human activated protein C, in adult patients with severe sepsis, is notable in that it is the first trial to show a reduction in 28-day all-cause mortality in the intent-to-treat population compared with the placebo group. When assessing a new intervention, patient exclusion criteria are important considerations in evaluating the evidence from a controlled clinical trial. Appropriate patient selection will be a key factor in the use of this newly approved therapeutic agent to treat severe sepsis. A review of the exclusion criteria used in the PROWESS trial should provide clinicians with a way of differentiating those patients in the critical care setting who will benefit most from treatment with drotrecogin alfa (activated) from those who should not be treated.
authors.affiliation: Pulmonary Medicine, Wake Forest University School of Medicine, 3rd Floor, Gray Building, 3325 Silas Creek Parkway, Winston-Salem, NC 27103, USA. pemorris@wfubmc.edu
authors.forename: Peter E
authors.initials: PE
authors.lastname: Morris
authors.forename: R Bruce
authors.initials: RB
authors.lastname: Light
authors.forename: Gary E
authors.initials: GE
authors.lastname: Garber
mesh_terms: D018806:APACHE; D000328:Adult; D000890:Anti-Infective Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000627:therapeutic use*; D002986:Clinical Trials as Topic / Q000379:methods; D015897:Comorbidity; D017277:Drug Approval / Q000458:organization & administration; D005343:Fibrinolytic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D006470:Hemorrhage / Q000139:chemically induced / Q000517:prevention & control*; D006801:Humans; D018579:Patient Selection; D011486:Protein C / Q000009:adverse effects / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use*; D012307:Risk Factors; D018746:Systemic Inflammatory Response Syndrome / Q000188:drug therapy* / Q000453:epidemiology; D014481:United States
chemical_list: D000890:Anti-Infective Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D005343:Fibrinolytic Agents; D011486:Protein C; D011994:Recombinant Proteins; C421124:drotrecogin alfa activated