Recombinant Factor for Variceal Bleeding in Patients with Cirrhosis

Previous studies have suggested that recombinant factor Vlla (rFVlla), an agent used to control bleeding, may reduce the number of failures and improve 24-hour bleeding control in Child-Pugh B and C-classified cirrhotic patients with variceal bleeding. Cirrhotic patients classified in class B or C under the Child-Pugh score have a one-year survival of 81 percent and 45 percent, respectively. The current trial, conducted by researchers from several European expert centers in liver disease, was aimed at determining the efficacy and safety of rFVlla in patients with advanced cirrhosis and active variceal bleeding.

To evaluate the therapy, 256 patients with advanced cirrhosis and active bleeding from gastroesophageal varices were randomized to placebo, 600 ìg/kg rFVlla or 300 ìg/kg rFVlla. In addition to standard treatment, study participants were given the first dose at baseline and after endoscopy; further doses were provided at two, eight, 14 and 20 hours. Researchers observed failure rates (bleeding) within 24 hours, failure to prevent clinically significantly rebleeding or death within five days. They also monitored adverse events and 42-day mortality.

While results showed that rFVlla as a treatment option did not improve efficacy of standard treatment, the treatment-related failures were lower than expected. While there was no significant difference in five-day mortality between groups (12% in the 600 ìg/kg rFVlla group vs.13% in placebo), the 42-day mortality was significantly lower in the 600 ìg/kg rFVlla group compared with placebo (15% in the 600 ìg/kg rFVlla group vs. 29% in placebo) and deaths due to bleeding were reduced (15% in the 600 ìg/kg rFVlla group vs. 40% in placebo). In addition, adverse events were comparable between groups.

"While there was no significant difference in the primary endpoint between treatment groups, the current trial did provide insight into the potential value and function of rFVlla," said Flemming Bendtsen, M.D., of Hvidovre Hospital in Hvidovre, Denmark, and co-author of this study. "Subgroup analysis of the two trials of rFVIIa in variceal bleeding are planned in order to identify characteristics of patients, who in the future may potentially benefit from this treatment."-American Gastroenterological Association