Efficacy and safety of recombinant human activated protein C for severe sepsis
Efficacy and safety of recombinant human activated protein C for severe sepsis
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DOI：
10.1097/00132586-200202000-00005
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发表时间：
2003
期刊：
影响因子：
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通讯作者：
Jeffrey Barkun;Nicolas V. Christou
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文献类型：
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作者：
Jeffrey Barkun;Nicolas V. Christou
目的：探讨活化重组蛋白C能否降低严重脓毒症患者28天全因死亡率。设计：随机、双盲、安慰剂对照试验。设置：多中心; 11个国家的164个中心。患者：该研究包括1690例患者（对照组840例，治疗组850例），根据临床数据已知或疑似感染，加上至少24小时内出现3种或3种以上全身炎症和脓毒症诱导的器官功能障碍体征。干预措施：患者被随机分配至静脉输注活化屈洛酮α（每小时24 μg/kg体重）共96小时或安慰剂组。主要结局指标：28天时任何原因导致的死亡。结果：治疗组死亡率为24.7%（95%CI 22%~ 28%），对照组死亡率为30.8%（95%CI 28%~ 34%）。活化蛋白C治疗与死亡相对风险降低19.4%（95% CI 6.6%-30.5%）和死亡绝对风险降低6.1%（p = 0.005）相关。曲托溴铵α活化组中3.5%的患者发生严重出血，而安慰剂组为2.0%（p = 0.06）。结论：活化蛋白C治疗显著降低了严重脓毒症的死亡率（绝对降低6.1%），但可能与出血风险增加相关（治疗组3.2%，p = 0.06）。
Objective: To find out whether activated recombinant protein C reduces the death rate from all causes at 28 days among patients with severe sepsis. Design: A randomized, doubleblind, placebo-controlled trial. Setting: Multicentre; 164 centres in 11 countries. Patients: The study comprised 1690 patients (840 in the control group and 850 in the treatment group) who had known or suspected infection based on clinical data, plus 3 or more signs of systemic inflammation and sepsis-induced organ dysfunction for at least 24 hours. Intervention: Patients were randomized to intravenous infusion of drotrecogin α activated (24 μg/kg body weight hourly) for a total of 96 hours or placebo. Main outcome measure: Death from any cause at 28 days. Results: The death rate in the treatment group was 24.7% (95% confidence interval [CI] 22%–28%) and in the control group was 30.8% (95% CI 28%–34%). Treatment with activated protein C was associated with a reduction in the relative risk of death of 19.4% (95% CI 6.6%–30.5%) and absolute reduction in the risk of death of 6.1% (p = 0.005). Serious bleeding occurred in 3.5% of patients in the drotrecogin α activated group compared with 2.0% in the placebo group (p = 0.06). Conclusion: Treatment with activated protein C significantly reduces mortality (6.1% absolute reduction) with severe sepsis but may be associated with an increased risk of bleeding (treatment group 3.2%, p = 0.06).