Division of Pulmonary and Critical Care Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Am J Respir Crit Care Med. 2011 Jun 1;183(11):1561-8. doi: 10.1164/rccm.201007-1167OC. Epub 2011 Feb 4.
Severe community-acquired pneumonia (sCAP) is a leading cause of death worldwide. Adjunctive therapies for sCAP are needed to further improve outcome. A systemic inhibitor of coagulation, tifacogin (recombinant human tissue factor pathway inhibitor) seemed to provide mortality benefit in the sCAP subgroup of a previous sepsis trial.
Evaluate the impact of adjunctive tifacogin on mortality in patients with sCAP.
A multicenter, randomized, placebo-controlled, double-blind, three-arm study was conducted from July 2005 to June 2008 at 188 centers in North and South America, Europe, South Africa, Asia, Australia, and New Zealand. Adults with sCAP were randomized to receive a continuous intravenous infusion of tifacogin 0.025 mg/kg/h, tifacogin 0.075 mg/kg/h, or matching placebo over 96 hours.
Severity-adjusted 28-day all-cause mortality. Of 2,138 randomized patients, 946, 238, and 918 received tifacogin 0.025 mg/kg/h, tifacogin 0.075 mg/kg/h, and placebo, respectively. Tifacogin 0.075 mg/kg/h was discontinued after the first interim analysis according to prespecified futility criterion. The 28-day all-cause mortality rates were similar between the 0.025 mg/kg/h (18%) and placebo groups (17.9%) (P = 0.56). Greater reduction in prothrombin fragment 1+2 and thrombin antithrombin complexes levels relative to baseline throughout the first 96 hours was found with tifacogin 0.025 mg/kg/h than with placebo. The incidence of adverse events and serious adverse events were comparable between the tifacogin 0.025 mg/kg/h and placebo groups.
Tifacogin showed no mortality benefit in patients with sCAP despite evidence of biologic activity.
严重社区获得性肺炎（sCAP）是全球范围内主要的致死病因。需要辅助疗法来进一步改善 sCAP 的预后。一种全身性凝血抑制剂，tifacogin（重组人组织因子途径抑制剂），在前瞻性脓毒症试验的 sCAP 亚组中似乎提供了死亡率获益。
评估辅助使用 tifacogin 对 sCAP 患者死亡率的影响。
一项多中心、随机、安慰剂对照、双盲、三臂研究于 2005 年 7 月至 2008 年 6 月在北美、南美、欧洲、南非、亚洲、澳大利亚和新西兰的 188 个中心进行。患有 sCAP 的成年人被随机分为三组，分别接受为期 96 小时的静脉持续输注 tifacogin（0.025mg/kg/h）、tifacogin（0.075mg/kg/h）或匹配的安慰剂。
校正严重程度的 28 天全因死亡率。2138 名随机患者中，946、238 和 918 名患者分别接受了 tifacogin 0.025mg/kg/h、tifacogin 0.075mg/kg/h 和安慰剂治疗。根据预先设定的无效标准，tifacogin 0.075mg/kg/h 在第一次中期分析后被停止。0.025mg/kg/h 组（18%）和安慰剂组（17.9%）的 28 天全因死亡率相似（P=0.56）。在整个 96 小时内，与基线相比，tifacogin 0.025mg/kg/h 组的凝血酶原片段 1+2 和凝血酶抗凝血酶复合物水平降低幅度更大。tifacogin 0.025mg/kg/h 组和安慰剂组的不良事件和严重不良事件发生率相当。
尽管有生物学活性的证据，但 tifacogin 对 sCAP 患者的死亡率没有获益。
