Drotrecogin alfa (activated) in the treatment of severe sepsis patients with multiple-organ dysfunction: Data from the PROWESS trial

Objective: Based on the results of the PROWESS trial the European Agency for the Evaluation of Medicinal Products has recently approved drotrecogin alfa (activated) for treatment of adult patients with severe sepsis and multiple-organ failure. We report study's data on efficacy and safety in patients with multiple-organ dysfunction. Design and setting: Randomized, double-blind, placebo-controlled, multicenter trial in 164 medical centers. Patients: 1271 patients (75.2% of the intention-to-treat population, n=1690) with multiple-organ dysfunction at study entry. Interventions: Drotrecogin alfa (activated) n=634, 24 mug/kg per hour for 96 h or placebo (n=637). Results Observed 28-day mortality was significantly lower with drug treatment than with placebo (26.5%vs. 33.9%), cardiovascular and respiratory organ dysfunction resolved more rapidly over the first 7 days, and serious bleeding events were more frequent (2.4% vs. 1.3%). Conclusions: Treatment with drotrecogin alfa (activated) significantly reduced 28-day mortality and more quickly resolved cardiovascular and respiratory organ dysfunction. The difference in serious bleeding event rates may be clinically significant; however, the overall benefit-risk profile appears favorable.