Objective: To demonstrate that drotrecogin alfa (activated) has an acceptable safety profile 1 yr from randomization.
Design: One-year follow-up of patients participating in a placebo-controlled clinical study of drotrecogin alfa (activated) in severe sepsis patients at low risk of death (the ADDRESS study).
Setting: The study was conducted at 516 hospitals in 34 countries.
Patients: The study included 2,640 patients.
Interventions: One-year follow-up was performed as an addendum to the placebo-controlled ADDRESS study. Treatment groups were compared using the chi-square test and Kaplan-Meier estimates.
Measurements and Main Results: Survival status at 1 yr was obtained for 90% of patients enrolled in the study (n = 2,376). The difference in mortality rate between drotrecogin alfa (activated) and placebo patients was numerically smaller at 1 yr (34.2% and 34.0%, respectively, p = .94) than at 28 days (18.5% and 17.0%, respectively, p = .34). In the subgroups defined by organ dysfunction class (single or multiple) and Acute Physiology and Chronic Health Evaluation II score (<25 or ≥25), the differences in mortality rate between treatment groups at 1 yr were consistent with those observed at 28 days; no significant differences in mortality rates between treatment groups were observed. No additional serious adverse events were reported during the period between hospital discharge and 1 yr.
Conclusions: No increased risk of death or evidence of harm at 1 yr was associated with drotrecogin alfa (activated) administration in patients with severe sepsis at lower risk of death.
From the Department of Critical Care Medicine, St. Luc University Hospital, UCL, Brussels, Belgium (PFL); Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Health Sciences Center, Denver, CO (EA); Lilly Research Centre, Eli Lilly and Company, Erl Wood, UK (JNJ); and Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN (BLT, NLC, FVB).
Supported, in part, by Eli Lilly and Company, Indianapolis, IN.
Drs. Abraham and Laterre either currently receive or previously have received research grant support from Eli Lilly and Company and either currently provide or previously have provided consulting services to Eli Lilly and Company. Dr. Booth and Mr. Trzaskoma are past employees and stockholders of Eli Lilly and Company. Dr. Janes and Ms. Correll are employees and stockholders of Eli Lilly and Company.
The study was conducted at 516 sites in 34 countries. A list of the participating institutions was published online in the full text article Abraham et al. N Engl J Med 2005; 353:1331–1342.
Address requests for reprints to: Pierre Francois Laterre, MD, St. Luc University Hospital, UCL, Medical-Surgical General ICU, Avenue Hippocrate 10, Brussels B-1200, Belgium.
Current address for Dr. Abraham: Department of Medicine, University of Alabama at Birmingham School of Medicine, Birmingham, AL. Current address for Dr. Booth: Novo Nordisk, Princeton, NJ. Current address for Mr. Trzaskoma: Genentech, South San Francisco, CA.