• bleeding;
  • bone marrow and stem cell transplantation;
  • recombinant activated factor VII

Summary. Background: Bleeding is a common complication following hematopoietic stem cell transplantation (HSCT) and standard hemostatic treatment is often ineffective. We conducted a multicentre, randomized trial of the efficacy and safety of activated recombinant factor VII (rFVIIa, NovoSeven®) in the treatment of bleeding following HSCT. Methods: 100 patients with moderate or severe bleeding (52 gastrointestinal; 26 hemorrhagic cystitis; seven pulmonary; one cerebral; 14 other) were included from days +2 to +180 post-transplant (97 allogeneic; three autologous) to receive seven doses of rFVIIa (40, 80 or 160 μg kg−1) or placebo every 6 h. The primary efficacy endpoint was the change in bleeding score between the first administration and 38 h. Results: No significant effect of increasing rFVIIa dose was observed on the primary endpoint. A post hoc analysis comparing each rFVIIa dose with placebo showed that 80 μg kg−1 rFVIIa improved the bleeding score at the 38 h time point (81% vs. 57%, P = 0.021). This effect was not seen at 160 μg kg−1. There were no differences in transfusion requirements across dose groups. There was no trend in the type or number of severe adverse events observed. Six thromboembolic events were observed in the active treatment groups: three during, and three following the 96-h observation period. Conclusions: Despite no overall effect of rFVIIa treatment on primary endpoint, post hoc analysis showed an improvement in the control of bleeding for 80 μg kg−1 rFVIIa vs. standard hemostatic treatment. The heterogeneity of the population may have contributed to the lack of an increasing effect with increased dose. Further trials should focus upon identifying the patient populations that may benefit from treatment with rFVIIa.