The team conducted a Phase III trial, in which they assessed whether treatment with drotrecogin alfa (recombinant human activated protein C) reduced the rate of death from any cause among patients with severe sepsis.
They reported their findings in this week's New England Journal of Medicine.
Patients with systemic inflammation and organ failure due to acute infection were enrolled in the randomized, double-blind trial. Each was assigned to receive an intravenous infusion of either placebo or drotrecogin alfa activated for a total duration of 96 hours.
The prospectively defined primary end-point was death from any cause, and was assessed 28 days after the start of the infusion.
Patients were monitored for adverse events; changes in vital signs, laboratory variables, and the results of microbiologic cultures; and the development of neutralizing antibodies against activated protein C.
A total of 1,690 patients were treated (840 in the placebo group and 850 in the drotrecogin alfa activated group).
The mortality rate was found to be 30.8% in the placebo group and 24.7% in the drotrecogin alfa activated group.
|Effect of activated drotrecogin alfa treatment:|
- Reduction in relative risk of death of 19.4%
- Absolute reduction in risk of death of 6.1%
|New England Journal of Medicine|
On the basis of the prospectively defined primary analysis, treatment with drotrecogin alfa activated was associated with a reduction in the relative risk of death of 19.4% and an absolute reduction in the risk of death of 6.1%.
The incidence of serious bleeding was higher in the drotrecogin alfa activated group than in the placebo group (3.5% vs. 2.0%).
Gordon Bernard, of the Vanderbilt University School of Medicine, Nashville, USA, concluded on behalf of the team, "Treatment with drotrecogin alfa activated significantly reduces mortality in patients with severe sepsis but may be associated with an increased risk of bleeding."
In an accompanying editorial, Michael A. Matthay, of the University of California, San Francisco, comments, "Activated protein C should be given to patients who meet all the inclusion criteria, including evidence of end-organ dysfunction with shock, acidosis, oliguria, or hypoxemia.
"The risks and benefits of the agent must be studied in patients at a higher risk of bleeding, in children, and in immunosuppressed patients, especially those with thrombocytopenia or neutropenia."
"The investigators have provided evidence that mortality can be reduced among patients with severe sepsis through the use of a new therapy that inhibits both the procoagulant and the inflammatory cascades," he concludes.