Drotrecogin alfa (Activated) in adults with septic shock

Ranieri, Marco V., Thompson, B. Taylor, Barie, Philip S., Dhainaut, Jean-François, Douglas, Ivor S., Finfer, Simon, Gårdlund, Bengt, Marshall, John C., Rhodes, Andrew, Artigas, Antonio, Payen, Didier, Tenhunen, Jyrki, Al-Khalidi, Hussein R., Thompson, Vivian, Janes, Jonathan, Macias, William L., Vangerow, Burkhard, Williams, Mark D., for the PROWESS-SHOCK Study Group and Reade, Michael (2012) Drotrecogin alfa (Activated) in adults with septic shock. New England Journal of Medicine, 366 22: 2055-2064. doi:10.1056/NEJMoa1202290

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Author Ranieri, Marco V.
Thompson, B. Taylor
Barie, Philip S.
Dhainaut, Jean-François
Douglas, Ivor S.
Finfer, Simon
Gårdlund, Bengt
Marshall, John C.
Rhodes, Andrew
Artigas, Antonio
Payen, Didier
Tenhunen, Jyrki
Al-Khalidi, Hussein R.
Thompson, Vivian
Janes, Jonathan
Macias, William L.
Vangerow, Burkhard
Williams, Mark D.
for the PROWESS-SHOCK Study Group
Reade, Michael
Title Drotrecogin alfa (Activated) in adults with septic shock
Journal name New England Journal of Medicine   Check publisher's open access policy
ISSN 0028-4793
Publication date 2012-05-31
Sub-type Article (original research)
DOI 10.1056/NEJMoa1202290
Open Access Status File (Publisher version)
Volume 366
Issue 22
Start page 2055
End page 2064
Total pages 10
Place of publication Boston, MA, United States
Publisher Massachusetts Medical Society
Language eng
Formatted 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.)
Keyword Multiple organ dysfunction
Placebo-controlled trial
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
School of Medicine Publications
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Created: Wed, 19 Dec 2012, 23:25:32 EST by Michael Reade on behalf of School of Medicine