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.


METHODS
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).


METHODS
The study was conducted at 516 hospitals in 34 countries.


METHODS
The study included 2,640 patients.


METHODS
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.


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.
Laterre
Pierre-Francois
PF
Department of Critical Care Medicine, St. Luc University Hospital, UCL, Brussels, Belgium.
Abraham
Edward
E
Janes
Jonathan M
JM
Trzaskoma
Benjamin L
BL
Correll
Nancy L
NL
Booth
Frank V
FV
D018806:APACHE; D000890:Anti-Infective Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D011486:Protein C / Q000009:adverse effects / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D018805:Sepsis / Q000188:drug therapy* / Q000401:mortality; D016019:Survival Analysis
D000890:Anti-Infective Agents; D011486:Protein C; D011994:Recombinant Proteins; C421124:drotrecogin alfa activated