Introduction
Upper gastrointestinal bleeding (UGIB) is a severe and frequent complication of cirrhosis. Preliminary results show that rFVIIa may reduce bleeding in cirrhotic patients. This trial aimed to determine the efficacy and safety of rFVIIa in cirrhotic patients with variceal and nonvariceal UGIB.
Methods
Two hundred and forty-five cirrhotic patients (Child–Pugh < 13; Child–Pugh A = 20%, B = 52%, C = 28%) with UGIB (variceal = 66%, nonvariceal = 34%) were equally randomized to receive eight doses of 100 μg/kg rFVIIa or placebo in addition to pharmacologic and endoscopic treatment. The primary composite endpoint was the failure to control UGIB within 24 hours postdosing, or failure to prevent rebleeding between 24 hours and day 5, or death within 5 days.
Results
Baseline characteristics were similar between the two groups. Results of primary and exploratory analyses are presented in Table 1. In the subgroup of Child–Pugh B and C variceal bleeders, significantly fewer patients in the rFVIIa-treated group failed on the primary composite endpoint (P = 0.03) and the 24 hour-bleeding control endpoint (P = 0.01) compared with placebo. rFVIIa did not improve the efficacy of standard treatment in Child–Pugh A cirrhotic patients, and no significant effect was found when analysing all applicable patients. Incidences of adverse events including thromboembolic events were similar, and there were no significant differences in 5-day or 42-day mortality.
Table 1.
| Placebo | rFVIIa | P | |
|---|---|---|---|
| Failure on composite endpoint | |||
| All patients | 19/123 | 16/122 | 0.72 |
| Variceal bleeders | 16/82 | 8/79 | 0.12 |
| Variceal bleeders Child B–C | 15/65 | 5/63 | 0.03 |
| Failure to control acute bleeding (within 24 hours) | |||
| Variceal bleeders | 8/82 | 2/79 | 0.10 |
| Variceal bleeders Child B–C | 7/65 | 3/63 | 0.01 |
| Failure to prevent rebleeding (24 hours-day 5) | |||
| Variceal bleeders | 9/82 | 5/79 | 0.40 |
| Variceal bleeders Child B–C | 8/65 | 3/63 | 0.13 |
| Failure to control acute bleeding or failure to prevent rebleeding within 5 days | |||
| Variceal bleeders | 13/82 | 6/79 | 0.14 |
| Variceal bleeders Child B–C | 12/65 | 3/63 | 0.03 |
Values are shown as failures/number of patients.
Conclusions
Exploratory analyses in Child–Pugh B and C cirrhotic patients indicated that administration of rFVIIa was safe and significantly reduced the proportion of patients who failed to control variceal bleeding. Further studies are needed to verify these findings.