A randomized, double-blind comparison of two dosage levels of recombinant factor VIIa in the treatment of joint, muscle and mucocutaneous haemorrhages in persons with haemophilia A and B, with and without inhibitors

Recombinant factor VIIa (rFVIIa) was developed to provide an improved procoagulant component capable of 'by-passing' inhibitor antibodies in the treatment of haemophilic patients. The primary objective of this study was to compare the efficacy of two dosage regimens of rFVIIa (given intravenously at periodic intervals) in the treatment of joint, muscle and mucocutaneous haemorrhages in persons with haemophilia A and B with and without inhibitors. The study was designed as a randomized, double-blind, parellel group, international multicenter trial. Patients were randomly allocated to treatment A: 35 μ kg^-1 or B: 70 μ kg^-1, in blocks of 2. Within each block, one patient was assigned to the 35 μ kg^-1 dosing regimen and the other to 70 μ kg^-1 dose. One hundred and fifty subjects from 20 sites were screened for this study and 116 had baseline assessments. Of these, 84 were treated on the protocol and 32 were not treated in the study, in most cases because they did not return to the clinic with an eligible bleeding episode. One hundred and seventy-nine bleeding episodes were treated, of which 145 (81%) were acute haemarthroses. Both treatments were efficacious, with 71% having an excellent (59% and 60%) or effective (12% and 11%) response. Overall, the mean and median number of doses given per episode of joint bleeding were 3.1 and 2, respectively. The mean number of doses was 3.1 for the 70 μ kg^-1 group and 2.7 for the 35 μ kg^-1 group (P value = 0.142). The study concluded that rFVIIa in a dosage of 35 μ kg^-1 or 70 μ kg^-1 is both safe and reasonably effective in the treatment of joint or muscle haemorrhages in haemophilic patients with inhibitor antibodies to factor VIII or factor IX. It is concluded that the appropriate dose for the treatment of joint and peripheral muscle bleeding in haemophilic patients with inhibitors is 35-70 μ kg^-1 given at 2-3 h intervals until haemostasis is achieved.