Effects of drotrecogin alfa (activated) in human endotoxemia.

Andre C Kalil, Susette M. Coyle, John Y Um, Steven P. LaRosa, Mary Ann Turlo, Steve E. Calvano, David P. Sundin, David R. Nelson, Stephen F. Lowry

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)222-229
Number of pages8
JournalShock (Augusta, Ga.)
Volume21
Issue number3
DOIs
StatePublished - Jan 1 2004

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Endotoxemia
Endotoxins
Sepsis
Clinical Trials
Phase III Clinical Trials
Pharmaceutical Preparations
Healthy Volunteers
Arterial Pressure
Anti-Inflammatory Agents
Biomarkers
Placebos
drotrecogin alfa activated
Survival

ASJC Scopus subject areas

  • Emergency Medicine
  • Critical Care and Intensive Care Medicine

Cite this

Kalil, A. C., Coyle, S. M., Um, J. Y., LaRosa, S. P., Turlo, M. A., Calvano, S. E., ... Lowry, S. F. (2004). Effects of drotrecogin alfa (activated) in human endotoxemia. Shock (Augusta, Ga.), 21(3), 222-229. https://doi.org/10.1097/01.shk.0000116778.27924.79

Effects of drotrecogin alfa (activated) in human endotoxemia. / Kalil, Andre C; Coyle, Susette M.; Um, John Y; LaRosa, Steven P.; Turlo, Mary Ann; Calvano, Steve E.; Sundin, David P.; Nelson, David R.; Lowry, Stephen F.

In: Shock (Augusta, Ga.), Vol. 21, No. 3, 01.01.2004, p. 222-229.

Research output: Contribution to journalArticle

Kalil, AC, Coyle, SM, Um, JY, LaRosa, SP, Turlo, MA, Calvano, SE, Sundin, DP, Nelson, DR & Lowry, SF 2004, 'Effects of drotrecogin alfa (activated) in human endotoxemia.', Shock (Augusta, Ga.), vol. 21, no. 3, pp. 222-229. https://doi.org/10.1097/01.shk.0000116778.27924.79
Kalil, Andre C ; Coyle, Susette M. ; Um, John Y ; LaRosa, Steven P. ; Turlo, Mary Ann ; Calvano, Steve E. ; Sundin, David P. ; Nelson, David R. ; Lowry, Stephen F. / Effects of drotrecogin alfa (activated) in human endotoxemia. In: Shock (Augusta, Ga.). 2004 ; Vol. 21, No. 3. pp. 222-229.
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