"Drotrecogin Alfa (Activated) in Adults with Septic Shock".The New England Journal of Medicine. 2012.

Clinical Question

Does drotrecogin alfa (activated) (DrotAA) reduce mortality in adults with septic shock?

Bottom Line

Drotrecogin alfa (activated) did not significantly reduce mortality at 28 or 90 days compared to placebo in adults with septic shock.

Major Points

Guidelines

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.

Design

Multicenter, double-blind, placebo-controlled, randomized trial.

Population

Included 1697 adult patients with infection, systemic inflammation, and shock, receiving a threshold dose of fluids and vasopressors for at least 4 hours.

Interventions

Patients randomly assigned to receive DrotAA (24 μg per kg per hour) or placebo for 96 hours.

Outcomes

The primary outcome was death from any cause at 28 days after randomization.

Major Points

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).

Criticisms

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.

Funding

The study was funded by Eli Lilly.

Further Reading

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.