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Liver Failure/Cirrhosis/Portal Hypertension
Recombinant factor VIIa for variceal bleeding in patients with advanced cirrhosis: A randomized, controlled trial†
Article first published online: 14 JAN 2008
Copyright © 2008 American Association for the Study of Liver Diseases
Volume 47, Issue 5, pages 1604–1614, May 2008
How to Cite
Bosch, J., Thabut, D., Albillos, A., Carbonell, N., Spicak, J., Massard, J., D'Amico, G., Lebrec, D., de Franchis, R., Fabricius, S., Cai, Y. and Bendtsen, F. (2008), Recombinant factor VIIa for variceal bleeding in patients with advanced cirrhosis: A randomized, controlled trial. Hepatology, 47: 1604–1614. doi: 10.1002/hep.22216
Potential conflict of interest: Drs. Bendtsen and D'Amico adivse Novo Nordisk. Dr. de Franchis is a consultant for Novo Nordisk.
- Issue published online: 24 APR 2008
- Article first published online: 14 JAN 2008
- Accepted manuscript online: 14 JAN 2008 12:00AM EST
- Manuscript Accepted: 20 DEC 2007
- Manuscript Received: 13 JUL 2007
- Novo Nordisk A/S, 2880 Bagsvaerd, Denmark
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 μg/kg rFVIIa (200 + 4× 100 μg/kg); or 300 μg/kg rFVIIa (200 + 100 μg/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 μg/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 μg/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. Conclusion: 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. (HEPATOLOGY 2008.)