Evidence-Based Answers

Evidence Central™ is an integrated web and mobile solution that helps clinicians quickly answer etiology, diagnosis, treatment, and prognosis questions using the latest evidence-based research.


Evidence Central for Mobile Devices

Evidence Central iOS iPhone iPad Android

Evidence Central from Unbound Medicine, available for iOS® and Android™, is optimized for each platform and features superior navigation, so answers are easy to find at the bedside or anywhere they’re needed. Learn More

Word of the Day

Recombinant human activated Protein C does not reduce mortality in patients with septic shock (PROWESS-SHOCK)

Clinical Question:
Does the use of drotrecogin alfa decrease mortality in patients with severe septic shock?

Bottom Line:
Recombinant human activated Protein C does not improve mortality in critically ill patients with septic shock. (LOE = 1b)

Ranieri VM, Thompson BT, Barie PS et al. Drotrecogin alfa (activated) in adults with septic shock. N Engl J Med 2012;366:2055-64.  [PMID:22616830]

Study Design:
Randomized controlled trial (double-blinded)



Inpatient (ICU only)

Current evidence for the efficacy of recombinant human activated Protein C, or drotrecogin alfa (DrotAA), in the treatment of septic shock is inconclusive. Using concealed allocation, these investigators randomized critically ill adults with septic shock requiring vasopressors to receive either an intravenous infusion of DrotAA at 24 ug/kg/hour for 96 hours (n=852) or matching placebo (n=845). Enrolled patients had a mean age of 63 years and the primary sites of infection were lung or abdomen. The majority had high severity of illness with 97% of patients showing evidence of multiorgan dysfunction. Analysis was by intention-to-treat and follow up was complete for 99% of the patients. There was no significant difference in mortality at 28 days or 90 days between the two groups. Analysis of data in prespecified subgroups, e.g. patients with acute respiratory distress syndrome, recent surgery, or higher Acute Physiology and Chronic Health Evaluation (APACHE) II scores, also showed lack of benefit of the study drug. While the DrotAA group did have more non-serious bleeding events when compared with the placebo group (8.6% vs. 4.8%, p=0.002), there was no difference in serious bleeding rates.


Site Licenses

Site license

Site Licenses are available for schools, universities, hospitals, government agencies, and companies. For more information, contact us.