Drotrecogin alfa (activated) in adults with septic shock.

Abstract

BACKGROUND:

There have been conflicting reports on the efficacy of recombinant human activated protein C, or drotrecogin alfa (activated) (DrotAA), for the treatment of patients with septic shock.

METHODS:

In this randomized, double-blind, placebo-controlled, multicenter trial, we assigned 1697 patients with infection, systemic inflammation, and shock who were receiving fluids and vasopressors above a threshold dose for 4 hours to receive either DrotAA (at a dose of 24 μg per kilogram of body weight per hour) or placebo for 96 hours. The primary outcome was death from any cause 28 days after randomization.

RESULTS:

At 28 days, 223 of 846 patients (26.4%) in the DrotAA group and 202 of 834 (24.2%) in the placebo group had died (relative risk in the DrotAA group, 1.09; 95% confidence interval [CI], 0.92 to 1.28; P=0.31). At 90 days, 287 of 842 patients (34.1%) in the DrotAA group and 269 of 822 (32.7%) in the placebo group had died (relative risk, 1.04; 95% CI, 0.90 to 1.19; P=0.56). Among patients with severe protein C deficiency at baseline, 98 of 342 (28.7%) in the DrotAA group had died at 28 days, as compared with 102 of 331 (30.8%) in the placebo group (risk ratio, 0.93; 95% CI, 0.74 to 1.17; P=0.54). Similarly, rates of death at 28 and 90 days were not significantly different in other predefined subgroups, including patients at increased risk for death. Serious bleeding during the treatment period occurred in 10 patients in the DrotAA group and 8 in the placebo group (P=0.81).

CONCLUSIONS:

DrotAA did not significantly reduce mortality at 28 or 90 days, as compared with placebo, in patients with septic shock. (Funded by Eli Lilly; PROWESS-SHOCK ClinicalTrials.gov number, NCT00604214.).

• Authors: V Marco Ranieri, B Taylor Thompson, Philip S Barie, Jean-François Dhainaut, Ivor S Douglas, Simon Finfer, Bengt Gårdlund, John C Marshall, Andrew Rhodes, Antonio Artigas, Didier Payen, Jyrki Tenhunen, Hussein R Al-Khalidi, Vivian Thompson, Jonathan Janes, William L Macias, Burkhard Vangerow, Mark D Williams, PROWESS-SHOCK Study Group
• Journal: The New England journal of medicine (N Engl J Med) Vol. 366 Issue 22 Pg. 2055-64 (May 31 2012) ISSN: 1533-4406 [Electronic] United States
• PMID: 22616830 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Infective Agents
• Protein C
• Recombinant Proteins
• drotrecogin alfa activated

Topics

• Adult
• Anti-Infective Agents (therapeutic use)
• Double-Blind Method
• Drug Therapy, Combination
• Humans
• Kaplan-Meier Estimate
• Odds Ratio
• Protein C (therapeutic use)
• Protein C Deficiency (complications, mortality)
• Recombinant Proteins (therapeutic use)
• Shock, Septic (complications, drug therapy, mortality)
• Treatment Failure