Drotrecogin alfa (activated) in the treatment of severe sepsis patients with multiple-organ dysfunction: Data from the PROWESS trial

被引:114
作者
Dhainaut, JF
Laterre, PF
Janes, JM
Bernard, GR
Artigas, A
Bakker, J
Riess, H
Basson, BR
Charpentier, J
Utterback, BG
Vincent, JL
机构
[1] Univ Paris 05, Cochin Inst, Cochin Port Royal Med Sch, Cochin Hosp APHP,Dept Intens Care, F-75679 Paris 14, France
[2] Clin Univ St Luc, Dept Crit Care & Emergency Med, B-1200 Brussels, Belgium
[3] Eli Lilly & Co, Lilly Res Ctr, Windlesham, Surrey, England
[4] Vanderbilt Univ, Sch Med, Div Allergy, Nashville, TN 37212 USA
[5] Vanderbilt Univ, Sch Med, Div Pulm, Nashville, TN 37212 USA
[6] Vanderbilt Univ, Sch Med, Div Crit Care Med, Nashville, TN 37212 USA
[7] Univ Autonoma Barcelona, Inst Parc Tauli, Crit Care Ctr, Sabadell Hosp, Sabadell, Spain
[8] Isala Klin, Zwolle, Netherlands
[9] Humboldt Univ, Klinikum Charite, Med Klin Haematol & Onkol, Berlin, Germany
[10] Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA
[11] Free Univ Brussels, Erasme Hosp, Dept Intens Care, B-1050 Brussels, Belgium
关键词
Drotrecogin alfa (activated); activated protein C; xigris; recombinant proteins; sepsis; septic shock;
D O I
10.1007/s00134-003-1731-1
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
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 mug/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.
引用
收藏
页码:894 / 903
页数:10
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