Bosch Jaime, Thabut Dominique, Bendtsen Flemming, D'Amico Gennaro, Albillos Agustín, González Abraldes Juan, Fabricius Soeren, Erhardtsen Elisabeth, de Franchis Roberto
Hospital Clinic, Liver Unit, Barcelona, Spain.
Gastroenterology. 2004 Oct;127(4):1123-30. doi: 10.1053/j.gastro.2004.07.015.
BACKGROUND & AIMS: Upper gastrointestinal bleeding (UGIB) is a severe and frequent complication of cirrhosis. Recombinant coagulation factor VIIa (rFVIIa) has been shown to correct the prolonged prothrombin time in patients with cirrhosis and UGIB. This trial aimed to determine efficacy and safety of rFVIIa in cirrhotic patients with variceal and nonvariceal UGIB.
A total of 245 cirrhotic patients (Child-Pugh < 13; Child-Pugh A = 20%, B = 52%, C = 28%) with UGIB (variceal = 66%, nonvariceal = 29%, bleeding source unknown = 5%) were randomized equally to receive 8 doses of 100 microg/kg rFVIIa or placebo in addition to pharmacologic and endoscopic treatment. The primary end point was a composite including: (1) failure to control UGIB within 24 hours after first dose, or (2) failure to prevent rebleeding between 24 hours and day 5, or (3) death within 5 days.
Baseline characteristics were similar between rFVIIa and placebo groups. rFVIIa showed no advantage over standard treatment in the whole trial population. Exploratory analyses, however, showed that rFVIIa significantly decreased the number of failures on the composite end point (P = 0.03) and the 24-hour bleeding control end point (P = 0.01) in the subgroup of Child-Pugh B and C variceal bleeders. There were no significant differences between rFVIIa and placebo groups in mortality (5- or 42-day) or incidence of adverse events including thromboembolic events.
Although no overall effect of rFVIIa was observed, exploratory analyses in Child-Pugh B and C cirrhotic patients indicated that administration of rFVIIa significantly decreased the proportion of patients who failed to control variceal bleeding. Dosing with rFVIIa appeared safe. Further studies are needed to verify these findings.
上消化道出血（UGIB）是肝硬化严重且常见的并发症。重组凝血因子VIIa（rFVIIa）已被证明可纠正肝硬化合并UGIB患者延长的凝血酶原时间。本试验旨在确定rFVIIa治疗肝硬化静脉曲张性和非静脉曲张性UGIB患者的疗效和安全性。
共有245例肝硬化合并UGIB患者（Child-Pugh评分<13；Child-Pugh A级占20%，B级占52%，C级占28%）（静脉曲张性出血占66%，非静脉曲张性出血占29%，出血来源不明占5%）被随机分为两组，除接受药物和内镜治疗外，分别接受8剂100μg/kg的rFVIIa或安慰剂。主要终点包括：（1）首剂后24小时内未能控制UGIB；（2）24小时至第5天未能预防再出血；（3）5天内死亡。
rFVIIa组和安慰剂组的基线特征相似。在整个试验人群中，rFVIIa与标准治疗相比无优势。然而，探索性分析表明，在Child-Pugh B级和C级静脉曲张出血亚组中，rFVIIa显著降低了复合终点的失败次数（P = 0.03）和24小时出血控制终点的失败次数（P = 0.01）。rFVIIa组和安慰剂组在死亡率（5天或42天）或不良事件发生率（包括血栓栓塞事件）方面无显著差异。
虽然未观察到rFVIIa的总体效果，但对Child-Pugh B级和C级肝硬化患者的探索性分析表明，给予rFVIIa可显著降低未能控制静脉曲张出血患者的比例。rFVIIa给药似乎是安全的。需要进一步研究来验证这些发现。
