ADDRESS (ADministration of DRotrecogin alfa [activated] in Early stage Severe Sepsis) long-term follow-up: one-year safety and efficacy evaluation.

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 >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.