Reuters Health Information (2004-04-02): Factor VIIa reduces treatment failure in cirrhosis-related upper GI bleeding
Factor VIIa reduces treatment failure in cirrhosis-related upper GI bleeding
Last Updated: 2004-04-02 15:42:13 -0400 (Reuters Health)
BRUSSELS, Belgium (Reuters Health) - Administration of recombinant factor VIIa (rFVIIa) in patients with cirrhosis and upper gastrointestinal (GI) bleeding reduces the high risk of treatment failure compared with standard strategies alone. These results were presented here at the 24th International Symposium on Intensive Care and Emergency Medicine.
Dr. Dominique Thabut, Hospital Pitie-Salpetriere, Paris, and multicenter colleagues, randomized 245 patients with cirrhosis and a Child-Pugh score of less than 12 to treatment with rFVIIa or placebo. All patients had signs of active, acute upper GI bleeding, suspected to be of variceal origin, and needed hospitalization as well as volume replacement therapy.
"Endoscopy was scheduled within 12 hours of admission," the authors note, "and patients were [then] randomized to standard medical therapy and eight doses of 100 micrograms/kg rFVIIa or placebo."
The primary composite endpoint was failure to control the upper GI bleed within 24 hours of the first dose of rFVIIa; failure to prevent rebleeding between 24 hours and 5 days, or death within 5 days.
Exploratory analysis of patients with variceal bleeding and Child-Pugh grade B or C score showed that significantly fewer patients treated with rFVIIa compared with placebo controls failed on the composite endpoint (p = 0.03), as well as on the 24-hour bleeding control endpoint (p = 0.01).
Specifically, only 8% of patients or 5 out of 62 variceal bleeders with a Child-Pugh score of B or C were considered treatment failures according to the primary composite endpoint, compared with 23% of placebo controls.
In the same group of variceal bleeders with a Child-Pugh B or C score, control of bleeding within 24 hours was achieved in all patients treated with rFVIIa, compared with an 11% failure rate in placebo controls. There was also a nonsignificant trend towards the prevention of rebleeding between 24 hours and 5 days, with 5% of those treated with rFVIIa not achieving this endpoint, versus 13% for placebo patients.
However, treatment with rFVIIa had no effect on the incidence of active bleeding at first endoscopy or on mortality at 5 days and at 42 days. Treatment also did not affect transfusion requirements, the number of emergency elective procedures or duration of hospitalization. No significant differences in adverse event rates were observed between the rFVIIa and placebo groups, and no clinically relevant changes in hematology or blood chemistry were observed either.
Upper GI bleeding is a severe and frequent complication of cirrhosis, with recurrence of rebleeding in 40% of cases within the first 6 weeks, the authors note. The findings of this initial trial of rFVIIa suggest it can be safely used in this setting.