Jean-François Dhainaut1, Pierre-François Laterre2, Jonathan M Janes3, Gordon R Bernard4, Antonio Artigas5, Jan Bakker6, Hanno Riess7, Bruce R Basson8, Julien Charpentier9, Barbara G Utterback8, Jean-Louis Vincent10. 1. Department of Intensive Care, Cochin Hospital AP-HP, Cochin Institute, Cochin Port-Royal Medical School, Paris V University, 27 rue due Faubourg Saint Jacques, 75679, Paris cedex 14, France. jean-francois.dhainaut@cch.ap-hop-paris.fr. 2. Department of Critical Care and Emergency Medicine, Cliniques Universitaires St. Luc, Brussels, Belgium. 3. Lilly Research Centre, Eli Lilly & Co. Ltd., Erl Wood Manor, Surrey, UK. 4. Divisions of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University School of Medicine, Nashville, Tenn., USA. 5. Critical Care Center, Sabadell Hospital, University Institute parc Tauli, Autonomous University of Barcelona, Sabadell, Spain. 6. Isala Klinieken, Zwolle, The Netherlands. 7. Universitätsklinikum Charité,Medizinische Klinik für Haematologie und Onkologie, Humbolt Universität, Berlin, Germany. 8. Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Ind., USA. 9. Department of Intensive Care, Cochin Hospital AP-HP, Cochin Institute, Cochin Port-Royal Medical School, Paris V University, 27 rue due Faubourg Saint Jacques, 75679, Paris cedex 14, France. 10. Department of Intensive Care, Erasme University Hospital, Free University of Brussels, Brussels, Belgium.
Abstract
OBJECTIVE: Based on the results of the PROWESS trial the European Agency for the Evaluation of Medicinal Products has recently approved drotrecogin alfa (activated) for treatment of adult patients with severe sepsis and multiple-organ failure. We report study's data on efficacy and safety in patients with multiple-organ dysfunction. DESIGN AND SETTING: Randomized, double-blind, placebo-controlled, multicenter trial in 164 medical centers. PATIENTS: 1271 patients (75.2% of the intention-to-treat population, n=1690) with multiple-organ dysfunction at study entry. INTERVENTIONS:Drotrecogin alfa (activated) n=634, 24 micro g/kg per hour for 96 h or placebo ( n=637). RESULTS: Observed 28-day mortality was significantly lower with drug treatment than with placebo (26.5%vs. 33.9%), cardiovascular and respiratory organ dysfunction resolved more rapidly over the first 7 days, and serious bleeding events were more frequent (2.4% vs. 1.3%). CONCLUSIONS: Treatment with drotrecogin alfa (activated) significantly reduced 28-day mortality and more quickly resolved cardiovascular and respiratory organ dysfunction. The difference in serious bleeding event rates may be clinically significant; however, the overall benefit-risk profile appears favorable.
RCT Entities:
OBJECTIVE: Based on the results of the PROWESS trial the European Agency for the Evaluation of Medicinal Products has recently approved drotrecogin alfa (activated) for treatment of adult patients with severe sepsis and multiple-organ failure. We report study's data on efficacy and safety in patients with multiple-organ dysfunction. DESIGN AND SETTING: Randomized, double-blind, placebo-controlled, multicenter trial in 164 medical centers. PATIENTS: 1271 patients (75.2% of the intention-to-treat population, n=1690) with multiple-organ dysfunction at study entry. INTERVENTIONS: Drotrecogin alfa (activated) n=634, 24 micro g/kg per hour for 96 h or placebo ( n=637). RESULTS: Observed 28-day mortality was significantly lower with drug treatment than with placebo (26.5%vs. 33.9%), cardiovascular and respiratory organ dysfunction resolved more rapidly over the first 7 days, and serious bleeding events were more frequent (2.4% vs. 1.3%). CONCLUSIONS: Treatment with drotrecogin alfa (activated) significantly reduced 28-day mortality and more quickly resolved cardiovascular and respiratory organ dysfunction. The difference in serious bleeding event rates may be clinically significant; however, the overall benefit-risk profile appears favorable.
Authors: William L Macias; Jean-Francois Dhainaut; Sau Chi Betty Yan; Jeffrey D Helterbrand; Mary Seger; Gerald Johnson; David S Small Journal: Clin Pharmacol Ther Date: 2002-10 Impact factor: 6.875
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