Recombinant coagulation factor VIIa in major liver resection -: A randomized, placebo-controlled, double-blind clinical trial

Background: Prevention of bleeding episodes in noncirrhotic patients undergoing partial hepatectomy remains unsatisfactory in spite of improved surgical techniques. The authors conducted a randomized, placebo-controlled, double-blind trial to evaluate the hemostatic effect and safety of recombinant factor VIIa (rFVIIa) in major partial hepatectomy. Methods: Two hundred four noncirrhotic patients were equally randomized to receive either 20 or 80 mug/kg rFVIIa or placebo. Partial hepatectomy was performed according to local practice at the participating centers. Patients were monitored for 7 days after surgery. Key efficacy parameters were perioperative erythrocyte requirements (using hematocrit as the transfusion trigger) and blood loss. Safety assessments included monitoring of coagulation-related parameters and Doppler examination of hepatic vessels and lower extremities. Results: The proportion of patients who required perioperative red blood cell transfusion (the primary endpoint) was 37% (23 of 63) in the placebo group, 41% (26 of 63) in the 20-mug/kg group, and 25% (15 of 59) in the 80-mug/kg dose group (logistic regression model; P = 0.09). Mean erythrocyte requirements for patients receiving erythrocytes were 1,024 nil with placebo, 1,354 nil with 20 mug/kg rFVIIa, and 1,036 nil with 80 mug/kg rFVIIa (P = 0.78). Mean intraoperative blood loss was 1,422 nil with placebo, 1,372 nil with 20 mug/kg rFVIIa, and 1,073 nil with 80 mug/kg rFVIIa (P = 0.07). The reduction in hematocrit during surgery was smallest in the 80-mug/kg group, with a significant overall effect of treatment (P = 0.04). Conclusions: Recombinant factor VIIa dosing did not result in a statistically significant reduction in either the number of patients transfused or the volume of blood products administered. No safety issues were identified.