Gårdlund B
Department of Infectious Diseases, Karolinska University Hospital Huddinge, Stockholm, Sweden.
Acta Anaesthesiol Scand. 2006 Sep;50(8):907-10. doi: 10.1111/j.1399-6576.2006.01086.x.
Drotrecogin alfa (activated) or recombinant human activated protein C (rhAPC) has been registered for use as adjuvant treatment in severe sepsis since 2001 under the trade name Xigris essentially based on the results from one large clinical trial (the PROWESS trial). In a recently published second randomized clinical trial (the ADDRESS trial), enrolling patients with severe sepsis but with less risk of death, no effect of the treatment was shown, not even a trend to a positive effect in the subgroup of patients with a high risk of death that would match the present prescription label for Xigris. In addition, a large randomized, placebo-controlled trial with rhAPC in paediatric sepsis has recently been terminated prematurely because of lack of efficacy. Altogether, the robustness of the data supporting the use of rhAPC in treating patients with severe sepsis may indeed be questioned. A confirmatory clinical trial is required before rhAPC can be used with confidence. The side-effects and the cost of rhAPC are well documented but its efficacy is not.
自2001年以来，重组人活化蛋白C（rhAPC），即活化蛋白C（Drotrecogin alfa），已以商品名Xigris注册用于严重脓毒症的辅助治疗，这主要基于一项大型临床试验（PROWESS试验）的结果。在最近发表的第二项随机临床试验（ADDRESS试验）中，纳入了死亡风险较低的严重脓毒症患者，结果显示该治疗没有效果，甚至在死亡风险较高的患者亚组中也没有出现与当前Xigris处方标签相符的积极效果趋势。此外，最近一项在儿童脓毒症中使用rhAPC的大型随机、安慰剂对照试验因缺乏疗效而提前终止。总之，支持使用rhAPC治疗严重脓毒症患者的数据的稳健性确实可能受到质疑。在能够放心使用rhAPC之前，需要进行一项验证性临床试验。rhAPC的副作用和成本有充分记录，但疗效却并非如此。
