"Drotrecogin Alfa (Activated) in Severe Sepsis".
The New England Journal of Medicine. 2001. 344(10):699-709.
PubMed • Full text • PDF
Clinical Question
Does treatment with drotrecogin alfa (activated) reduce mortality in patients with severe sepsis?
Bottom Line
Treatment with drotrecogin alfa (activated) significantly reduces mortality in patients with severe sepsis but may be associated with an increased risk of bleeding.
Major Points
Severe sepsis, a generalized inflammatory and procoagulant response to infection, results in a high rate of mortality despite advancements in critical care. Drotrecogin alfa (activated), or recombinant human activated protein C, has antithrombotic, antiinflammatory, and profibrinolytic properties. This phase 3 trial assessed its efficacy in reducing mortality rates in patients with severe sepsis.
Guidelines
No guidelines are discussed in this article.
Design
Randomized, double-blind, placebo-controlled, multicenter trial.
Population
Inclusion Criteria
- Known or suspected infection with clinical evidence
- Systemic inflammation and organ failure due to acute infection within 24 hours
- Treatment within 24 hours of meeting inclusion criteria
Exclusion Criteria
Not described in detail in the provided text.
Baseline Characteristics
- Demographics and severity of disease were similar between placebo and treatment groups.
Interventions
- Patients were randomly assigned to receive either placebo or drotrecogin alfa activated (24 μg/kg/hour) for 96 hours.
Outcomes
Primary Outcome
- Mortality from any cause at 28 days after the initiation of the infusion.
Secondary Outcomes
- Reduction in plasma D-dimer and serum interleukin-6 levels, indicating a reduced procoagulant state and decreased inflammation in the treatment group.
Criticisms
- Potential for increased risk of bleeding.
Funding
Supported by Eli Lilly.
Further Reading
The article would have sections on Design, Population, additional Criticisms, and other further reading references not provided in the abstract.