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Drotrecogin alfa (activated) improved mortality rates in severe sepsis
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Drotrecogin alfa (activated) reduced hospital mortality and increased bleeding rates in patients with severe sepsis, recent data suggest.
Researchers from the University of Nebraska Medical Center in Omaha and Beverly Hospital in Massachusetts conducted a meta-analysis and meta-regression study to analyze the effectiveness and safety of drotrecogin alfa (activated) (Xigris, Eli Lilly). According to information in the article, the drug has been under controversy since its approval.
The researchers searched six databases for experimental and analytical studies of drotrecogin alfa (activated). They identified nine controlled trials and 16 single-group studies in effectiveness analysis and 20 studies in safety analyses. The effectiveness studies included 47,223 patients and the safety studies included 8,245 patients.
Drotrecogin alfa (activated) was associated with an 18% reduction in hospital mortality (RR=0.822; 95% CI, 0.779-0.867). This reduction was similar to the reduction in the Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) trial, the phase 3, randomized, placebo-control trial on which approval of the drug was based. The rate of serious bleeding events among the studies was 5.6%, which was significantly higher than found in the PROWESS study.
In the meta-regression study, patients who had a higher severity of illness had a significantly lower risk for death if they received drotrecogin alfa. Serious bleeding outcomes did not differ according to severity.
“Compared with the PROWESS trial, real-life use of drotrecogin alfa (activated) was associated with higher hospital mortality rates in controlled and single-group studies and a similar and significant reduction in the risk of death,” the researchers wrote. “The risk of severe bleeding with drotrecogin alfa (activated) was greater in clinical practice than it was in the registration trial and seems to be because of off-label use rather than to treatment of patients with increased disease severity.”
References:
Kalil AC. Lancet Infect Dis. 2012;doi:10.1016/S1473-3099(12)70157-3.
Disclosures:
The researchers report financial relationships with Agennix, Artisan Pharma, AstraZeneca and Eisai.