"Drotrecogin Alfa (Activated) in Adults with Septic Shock".The New England Journal of Medicine. 2012.
Links to original sources: Wiki Journal Post Full Journal Article
Does drotrecogin alfa (activated) (DrotAA) reduce mortality in adults with septic shock?
Drotrecogin alfa (activated) did not significantly reduce mortality at 28 or 90 days compared to placebo in adults with septic shock.
Drotrecogin alfa (activated), a recombinant human activated protein C, was approved for severe sepsis treatment based on the PROWESS study, which suggested mortality benefits for certain patient subgroups with severe disease. However, subsequent studies raised doubts regarding its efficacy. The PROWESS-SHOCK study aimed to reassess the efficacy of DrotAA in adult patients with septic shock.
Drotrecogin alfa (activated) was approved for use in severe sepsis patients with a high risk of death. However, post-approval studies failed to demonstrate benefits for less severely ill adults and children, leading to further scrutiny and the need for this study.
Multicenter, double-blind, placebo-controlled, randomized trial.
Included 1697 adult patients with infection, systemic inflammation, and shock, receiving a threshold dose of fluids and vasopressors for at least 4 hours.
Patients randomly assigned to receive DrotAA (24 μg per kg per hour) or placebo for 96 hours.
The primary outcome was death from any cause at 28 days after randomization.
At 28 days, mortality was 26.4% in DrotAA group vs. 24.2% in the placebo group (relative risk 1.09; 95% CI, 0.92 to 1.28; P=0.31). Mortality at 90 days was 34.1% for DrotAA vs. 32.7% for placebo (relative risk 1.04; 95% CI, 0.90 to 1.19; P=0.56).
The study was limited by the lack of in-depth analysis of coagulation or inflammatory responses to the study drugs, which was available from previous trials. Mortality in the placebo group was lower than expected but similar to other contemporary studies.
The study was funded by Eli Lilly.
Full study details and additional analysis can be found at ClinicalTrials.gov (NCT00604214) and supplementary material can be accessed with the full text of the original article at NEJM.org.