Bosch Jaime, Thabut Dominique, Albillos Agustín, Carbonell Nicolas, Spicak Julius, Massard Julien, D'Amico Gennaro, Lebrec Didier, de Franchis Roberto, Fabricius Søren, Cai Yan, Bendtsen Flemming
Hepatic Hemodynamic Laboratory, Hospital Clinic and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), University of Barcelona, Spain.
Hepatology. 2008 May;47(5):1604-14. doi: 10.1002/hep.22216.
A beneficial effect of recombinant activated factor VII (rFVIIa) in Child-Pugh class B and C patients with cirrhosis who have variceal bleeding has been suggested. This randomized controlled trial assessed the efficacy and safety of rFVIIa in patients with advanced cirrhosis and active variceal bleeding. At 31 hospitals in an emergency setting, 256 patients (Child-Pugh > 8; Child-Pugh B = 26%, C = 74%) were randomized equally to: placebo; 600 microg/kg rFVIIa (200 + 4x 100 microg/kg); or 300 microg/kg rFVIIa (200 + 100 microg/kg). Dosing was intravenous at 0, 2, 8, 14, and 20 hours after endoscopy, in addition to standard vasoactive, prophylactic antibiotic, and endoscopic treatment. The primary composite endpoint consisted of failure to control 24-hour bleeding, or failure to prevent rebleeding or death at day 5. Secondary endpoints included adverse events and 42-day mortality. Baseline characteristics were comparable between groups. Administration of rFVIIa had no significant effect on the composite endpoint compared with placebo (P = 0.37). There was no significant difference in 5-day mortality between groups; however, 42-day mortality was significantly lower with 600 microg/kg rFVIIa compared with placebo (odds ratio 0.31, 95% confidence interval = 0.13-0.74), and bleeding-related deaths were reduced from 12% (placebo) to 2% (600 microg/kg). A marked heterogeneity in the failure rate in all treatment groups was observed across participating centers. Adverse events, including overall thromboembolic events, were comparable between groups.
Treatment with rFVIIa had no significant effect on the primary composite endpoint compared with placebo. Therefore, decision on the use of this hemostatic agent in acute variceal bleeding should be carefully considered, because results of this study do not support the routine use of rFVIIa in this setting. Adverse events were comparable across groups.
已有研究提示重组活化因子VII（rFVIIa）对Child-Pugh B级和C级肝硬化伴静脉曲张出血患者有有益作用。本随机对照试验评估了rFVIIa在晚期肝硬化伴活动性静脉曲张出血患者中的疗效和安全性。在31家医院的急诊环境中，256例患者（Child-Pugh评分>8分；Child-Pugh B级占26%，C级占74%）被随机均分为：安慰剂组；600μg/kg rFVIIa组（200 + 4×100μg/kg）；或300μg/kg rFVIIa组（200 + 100μg/kg）。除标准的血管活性药物、预防性抗生素和内镜治疗外，在内镜检查后0、2、8、14和20小时静脉给药。主要复合终点包括24小时出血控制失败、第5天预防再出血或死亡失败。次要终点包括不良事件和42天死亡率。各组基线特征具有可比性。与安慰剂相比，rFVIIa给药对复合终点无显著影响（P = 0.37）。各组间5天死亡率无显著差异；然而，与安慰剂相比，600μg/kg rFVIIa组42天死亡率显著降低（比值比0.31，95%置信区间 = 0.13 - 0.74），且出血相关死亡率从12%（安慰剂组）降至2%（600μg/kg组）。在所有参与中心观察到所有治疗组失败率存在明显异质性。包括总体血栓栓塞事件在内的不良事件在各组间具有可比性。
与安慰剂相比，rFVIIa治疗对主要复合终点无显著影响。因此，在急性静脉曲张出血中使用这种止血剂的决策应谨慎考虑，因为本研究结果不支持在此情况下常规使用rFVIIa。各组不良事件具有可比性。
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