Open AccessEffects of Drotrecogin Alfa (Activated) in Human Endotoxemia
Author(s) -
André C. Kalil,
Susette M. Coyle,
J. Um,
Steven P. LaRosa,
Mary Ann Turlo,
T. Steve E. Calvano,
David P. Sundin,
David R. Nelson,
Stephen F. Lowry
Publication year - 2004
Publication title -
shock
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.095
H-Index - 117
eISSN - 1540-0514
pISSN - 1073-2322
DOI - 10.1097/01.shk.0000116778.27924.79
Subject(s) - drotrecogin alfa , medicine , sepsis , placebo , clinical trial , antithrombotic , pharmacology , anesthesia , septic shock , severe sepsis , pathology , alternative medicine
In a phase III clinical trial, drotrecogin alfa (activated) was shown to improve survival and promote faster improvement of cardiovascular and respiratory dysfunction in patients with severe sepsis. To further examine mechanisms involved in the action of this drug, a healthy human endotoxin model was used. Healthy volunteers (eight per group) received drotrecogin alfa (activated) or placebo intravenously for 8 h in a randomized, double-blind, controlled manner. After 2 h of study drug infusion, endotoxin (2 ng/kg) was infused and measurement of physiologic responses and biomarkers continued for 24 h. Consistent with results from severe sepsis clinical trials, drotrecogin alfa (activated) improved mean arterial pressure during the period of infusion after endotoxin exposure. In contrast to severe sepsis clinical trials using drotrecogin alfa (activated) but similar to another human endotoxin study, no significant antithrombotic, profibrinolytic, or anti-inflammatory effects were observed. These results suggest a novel role for drotrecogin alfa (activated) in the human endotoxin model.