Recombinant factor VIIa for upper gastrointestinal bleeding in patients with cirrhosis: a randomized, double-blind trial.
OBJECTIVE
Upper gastrointestinal bleeding (UGIB) is a severe and frequent complication of cirrhosis. Recombinant coagulation factor VIIa (rFVIIa) has been shown to correct the prolonged prothrombin time in patients with cirrhosis and UGIB. This trial aimed to determine efficacy and safety of rFVIIa in cirrhotic patients with variceal and nonvariceal UGIB.


METHODS
A total of 245 cirrhotic patients (Child-Pugh < 13; Child-Pugh A = 20%, B = 52%, C = 28%) with UGIB (variceal = 66%, nonvariceal = 29%, bleeding source unknown = 5%) were randomized equally to receive 8 doses of 100 microg/kg rFVIIa or placebo in addition to pharmacologic and endoscopic treatment. The primary end point was a composite including: (1) failure to control UGIB within 24 hours after first dose, or (2) failure to prevent rebleeding between 24 hours and day 5, or (3) death within 5 days.


RESULTS
Baseline characteristics were similar between rFVIIa and placebo groups. rFVIIa showed no advantage over standard treatment in the whole trial population. Exploratory analyses, however, showed that rFVIIa significantly decreased the number of failures on the composite end point (P = 0.03) and the 24-hour bleeding control end point (P = 0.01) in the subgroup of Child-Pugh B and C variceal bleeders. There were no significant differences between rFVIIa and placebo groups in mortality (5- or 42-day) or incidence of adverse events including thromboembolic events.


CONCLUSIONS
Although no overall effect of rFVIIa was observed, exploratory analyses in Child-Pugh B and C cirrhotic patients indicated that administration of rFVIIa significantly decreased the proportion of patients who failed to control variceal bleeding. Dosing with rFVIIa appeared safe. Further studies are needed to verify these findings.
Bosch
Jaime
J
Hospital Clinic, Liver Unit, Barcelona, Spain. jbosch@medicina.ub.es
Thabut
Dominique
D
Bendtsen
Flemming
F
D'Amico
Gennaro
G
Albillos
Agustín
A
González Abraldes
Juan
J
Fabricius
Soeren
S
Erhardtsen
Elisabeth
E
de Franchis
Roberto
R
D000328:Adult; D000368:Aged; D004311:Double-Blind Method; D015942:Factor VIIa / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000188:drug therapy*; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000627:therapeutic use
D011994:Recombinant Proteins; D015942:Factor VIIa