1.
Effect of recombinant Factor VIIa on outcome of acute variceal bleeding: an individual patient based meta-analysis of two controlled trials
Bendtsen F, D'Amico G, Rusch E, de Franchis R, Andersen PK, Lebrec D, Thabut D, Bosch J
Journal of Hepatology. 2014;61((2)):252-9.
Abstract
BACKGROUND & AIMS Two randomized controlled studies have evaluated the effect of recombinant Factor VIIa (rFVIIa) on variceal bleeding in cirrhosis without showing significant benefit. The aim of the present study was to perform a meta-analysis of the two trials on individual patient data with special focus on high risk patients. METHODS The primary outcome measure was the effect of rFVIIa on a composite five day endpoint: failure to control bleeding, 5-day rebleeding or death. Analysis was based on intention to treat. High risk was defined as active bleeding on endoscopy while under vasoactive drug infusion and Child-Pugh score >8. RESULTS 497 patients were eligible for the meta-analysis; 308 (62%) had active variceal bleeding at endoscopy (oozing or spurting) and 283 of these had a Child-Pugh score >8. Analysis on the composite endpoint in all patients with bleeding from oesophageal varices did not show any beneficial treatment effect. However, failure rate for the primary composite end-point was significantly lower in treated patients with active bleeding at endoscopy (17%) compared to placebo (26%, p=0.049). This difference was highly significant in patients with Child-Pugh score >8 and active bleeding at endoscopy (rFVIIa 16%, placebo 27%; p=0.023). No significant treatment effect was found at 42 days. Five thromboembolic events occurred in rFVIIa treated patients compared to none in placebo treated patients. CONCLUSIONS The current meta-analysis shows a beneficial effect of rFVIIa on the primary composite endpoint of control of acute bleeding, prevention of rebleeding day 1-5 and 5-day mortality in patients with advanced cirrhosis and active bleeding from oesophageal varices at endoscopy. A major drawback of the treatment is a potential increased risk of arterial thrombo-embolic events. This treatment might be considered in patients with lack of control of bleeding after standard treatment.Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. RN 0 (Recombinant Proteins). 0 (recombinant FVIIa). EC 3-4-21-21 (Factor VIIa).
2.
Recombinant factor VIIa for variceal bleeding in patients with advanced cirrhosis: A randomized, controlled trial
Bosch J, Thabut D, Albillos A, Carbonell N, Spicak J, Massard J, D'Amico G, Lebrec D, de Franchis R, Fabricius S, et al
Hepatology (Baltimore, Md.). 2008;47((5):):1604-14.
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Abstract
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. 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.
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Comparison of outcome in patients with cirrhosis and ascites following treatment with albumin or a synthetic colloid: a randomised controlled pilot trail
Moreau R, Valla DC, Durand-Zaleski I, Bronowicki JP, Durand F, Chaput JC, Dadamessi I, Silvain C, Bonny C, Oberti F, et al
Liver International : Official Journal of the International Association for the Study of the Liver. 2006;26((1):):46-54.
Abstract
BACKGROUND The question of which colloid (albumin or synthetic colloids) used for plasma expansion following paracentesis or other complications requiring fluid loading in patients with cirrhosis remains controversial. AIMS To compare outcome and hospital-related cost in patients with cirrhosis treated with 20% human albumin with those treated with a synthetic colloid (3. 5% polygeline). METHODS The primary end point was occurrence of a first liver-related complication. RESULTS When the trial was prematurely discontinued because of safety concerns about bovine-derived products, 30 patients were assigned to receive albumin and 38 were assigned to receive a synthetic colloid. Sixty-three patients were included for ascites removal by paracentesis and five patients for ascites removal by paracentesis and renal impairment. The median time to first liver-related complication was not significantly longer in the albumin group (20 vs. 7 days). However, the total number of liver-related complications adjusted to a 100-day period was significantly lower in the albumin group. The median hospital cost for a 30-day period was significantly lower in the albumin group (1915 euros vs. 4612 euros). CONCLUSIONS In patients with cirrhosis and ascites, human albumin appears to be more effective in preventing liver-related complications than synthetic colloid. This may be associated with decreased hospital costs.
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Comparison of the effect of terlipressin and albumin on arterial blood volume in patients with cirrhosis and tense ascites treated by paracentesis: a randomised pilot study
Moreau R, Asselah T, Condat B, de Kerguenec C, Pessione F, Bernard B, Poynard T, Binn M, Grange JD, Valla D, et al
Gut. 2002;50((1):):90-4.
Abstract
BACKGROUND Patients with cirrhosis and tense ascites treated by paracentesis alone have a decrease in effective arterial blood volume after ascites removal. Although intravenous albumin is effective in preventing paracentesis induced decreased arterial blood volume, its clinical use is controversial. As paracentesis induces arteriolar vasodilation which plays a role in the development of decreased effective arterial blood volume, administration of a vasoconstrictor (terlipressin) could prevent circulatory alterations due to paracentesis. AIMS To perform a pilot study comparing the effects of terlipressin and albumin on effective arterial blood volume in patients with cirrhosis treated by paracentesis for tense ascites. METHODS Twenty patients with cirrhosis and tense ascites were randomly assigned to be treated by either paracentesis and terlipressin or paracentesis and albumin. Terlipressin (3 mg) or albumin (8 g/l of removed ascites) were administered on the day of paracentesis. Effective arterial blood volume was assessed by measuring plasma renin concentrations at baseline and on the day of hospital discharge (4-6 days after treatment). Decreased effective arterial blood volume was defined as an increase in plasma renin concentrations on the day of hospital discharge of more than 50% of baseline values. RESULTS Irrespective of the treatment group, mean values for plasma renin concentrations at hospital discharge did not differ from their respective baseline values (p=0.10). Baseline plasma levels of renin concentrations did not differ between the terlipressin and albumin groups (p=0.61). Changes from baseline in plasma renin concentrations did not differ between groups (p=0.39). Three patients in the terlipressin group and three in the albumin group developed decreased arterial blood volume. CONCLUSIONS This randomised pilot study suggests that terlipressin may be as effective as intravenous albumin in preventing a decrease in effective arterial blood volume in patients with cirrhosis treated by paracentesis for tense ascites.