WASHINGTON -- Recombinant clotting Factor VIIa should be used only as a last resort to treat variceal bleeding in patients with advanced cirrhosis, according to European researchers.
WASHINGTON, May 20 -- Recombinant clotting Factor VIIa should be used only as a last resort to treat variceal bleeding in patients with advanced cirrhosis, according to European researchers.
On the basis of a recent randomized, placebo-controlled trial, Factor VIIa "is only for rescue therapy" when other options have failed, said Flemming Bendtsen, M.D., of Hvidovre Hospital in Hvidovre, Denmark.
An earlier pilot study had suggested that the clotting factor was life-saving in patients with advanced cirrhosis, but the newest research failed to confirm that, Dr. Bendtsen told attendees at Digestive Disease Week here.
Indeed, he and colleagues from five other European countries found that there was no difference from placebo in controlling bleeding within 24 hours, preventing clinically significant re-bleeding, or lowering five-day mortality rates.
On the other hand, a high dose of the clotting factor did significantly reduce mortality at 42 days, one of the study's secondary endpoints, Dr. Bendtsen said.
The study compared placebo to two different doses of recombination Factor VIIa (300 or 600 micrograms per kilogram of body weight) in 256 patients with cirrhosis at Child-Pugh stage B or C, and greater than eight.
The first dose was given after endoscopy and subsequent doses in conjunction with standard therapy, Dr. Bendtsen said.
The only significant difference between the arms, he said, was 42-day mortality, which was lower for patients getting the 600-microgram dose of Factor VIIa.
Specifically, there were 13 deaths in the high-dose group, compared with 25 in the placebo group and 26 in the low-dose Factor VIIa group. The difference from placebo was significant at P=0.03.
Dr. Bendtsen said one possible reason for the null outcome of the 10-center clinical trial was that placebo patients did better than expected, so that differences were not significant.
Adverse events were comparable between groups and there was no significant difference in thromboembolic events overall, but 3 arterial thrombotic events occurred only in the Factor VIIa groups.
He and colleagues are currently performing a meta-analysis of the pilot study and the latest trial to see if a larger sample shows a positive effect for the clotting factor.
"One should wait for the results of the analysis of the two trials in combination before we can give strict conclusions," Dr. Bendtsen said.
Using Factor VIIa would be a "major leap in complexity and cost over what we typically use to treat variceal bleeding," said Jacquelyn Maher, M.D., of the Liver Center at the University of California at San Francisco.
Patients are often treated with fresh frozen plasma to increase serum levels of their clotting factors and "this is just a fancier way of doing that," said Dr. Maher, who was not involved in the research.
The approach "has appeal but also downsides," she said, including cost and the potential for thrombotic complications.
In the study presented by Dr. Bendtsen, there were three myocardial infarctions, all in the Factor VIIa groups, although the differences were not significant.