Holder Andre L, Huang David T
Crit Care. 2013 Mar 12;17(2):309. doi: 10.1186/cc12533.
Ranieri VM, Thompson BT, Barie PS, Dhainaut JF, Douglas IS, Finfer S, Gårdlund B, Marshall JC, Rhodes A, Artigas A, Payen D, Tenhunen J, Al-Khalidi HR, Thompson V, Janes J, Macias WL, Vangerow B, Williams MD: Drotrecogin alfa (activated) in adult patients with septic shock. N Engl J Med 2012, 366:2055-2064.
There have been conflicting reports on the efficacy of recombinant human activated protein C, or drotrecogin alfa (activated) (DrotAA), for the treatment of patients with septic shock.
To test the hypothesis that DrotAA, as compared with placebo, would reduce mortality in patients with septic shock.
A randomized, double-blind, placebo-controlled, multicenter trial, conducted from March 2008 through August 2011. Patients were followed until either 90 days or death.
Patients were enrolled from 208 sights in Europe, North and South America, Australia, New Zealand, and India.
Subjects included 1,697 patients with infection, systemic inflammation, and shock who were receiving fluids and vasopressors above a threshold dose for 4 hours.
DrotAA (at a dose of 24 μg per kilogram of body weight per hour) or placebo for 96 hours.
Death from any cause 28 days after randomization.
At 28 days, 223 of 846 patients (26.4%) in the DrotAA group and 202 of 834 (24.2%) in the placebo group had died (relative risk in the DrotAA group, 1.09; 95% confidence interval (CI), 0.92 to 1.28; P=0.31). At 90 days, 287 of 842 patients (34.1%) in the DrotAA group and 269 of 822 (32.7%) in the placebo group had died (relative risk, 1.04; 95% CI, 0.90 to 1.19; P=0.56). Among patients with severe protein C deficiency at baseline, 98 of 342 (28.7%) in the DrotAA group had died at 28 days, as compared with 102 of 331 (30.8%) in the placebo group (risk ratio, 0.93; 95% CI, 0.74 to 1.17; P=0.54). Similarly, rates of death at 28 and 90 days were not significantly different in other predefined subgroups, including patients at increased risk for death. Serious bleeding during the treatment period occurred in 10 patients in the DrotAA group and 8 in the placebo group (P=0.81).
DrotAA did not significantly reduce mortality at 28 or 90 days, as compared with placebo, in patients with septic shock.
拉涅利·V·M、汤普森·B·T、巴里·P·S、达伊诺·J·F、道格拉斯·I·S、芬弗·S、加尔隆德·B、马歇尔·J·C、罗兹·A、阿蒂加斯·A、帕扬·D、滕胡宁·J、阿尔-哈利迪·H·R、汤普森·V、杰恩斯·J、马西亚斯·W·L、万格罗·B、威廉姆斯·M·D：重组人活化蛋白C（即活化蛋白C）用于感染性休克成年患者的治疗。《新英格兰医学杂志》2012年，366卷：2055 - 2064页。
关于重组人活化蛋白C（即活化蛋白C，DrotAA）治疗感染性休克患者的疗效，已有相互矛盾的报道。
检验与安慰剂相比，活化蛋白C可降低感染性休克患者死亡率这一假设。
一项随机、双盲、安慰剂对照、多中心试验，于2008年3月至2011年8月进行。对患者随访至90天或直至死亡。
患者来自欧洲、南北美洲、澳大利亚、新西兰和印度的208个地点。
研究对象包括1697例患有感染、全身炎症反应和休克且接受液体和血管升压药治疗达阈值剂量4小时的患者。
活化蛋白C（剂量为每千克体重每小时24微克）或安慰剂，持续96小时。
随机分组后28天内任何原因导致的死亡。
在28天时，活化蛋白C组846例患者中有223例（26.4%）死亡，安慰剂组834例中有202例（24.2%）死亡（活化蛋白C组相对风险为1.09；95%置信区间[CI]为0.92至1.28；P = 0.31）。在90天时，活化蛋白C组842例患者中有287例（34.1%）死亡，安慰剂组822例中有269例（32.7%）死亡（相对风险为1.04；95% CI为0.90至1.19；P = 0.56）。在基线时严重蛋白C缺乏的患者中，活化蛋白C组342例中有98例（28.7%）在28天时死亡，而安慰剂组331例中有102例（30.8%）死亡（风险比为0.93；95% CI为0.74至1.17；P = 0.54）。同样，在其他预先定义的亚组中，包括死亡风险增加的患者，28天和90天的死亡率差异无统计学意义。治疗期间，活化蛋白C组有10例患者发生严重出血，安慰剂组有8例（P = 0.81）。
与安慰剂相比，活化蛋白C在感染性休克患者中28天或90天时并未显著降低死亡率。
