Objective. To assess the safety and efficacy of a fixed dose of recombinant activated factor VII (rFVIIa: NovoSeven®) in the home setting for mild to moderately severe joint, muscle, and mucocutaneous bleeding episodes in patients with haemophilia A or B with inhibitors. Design. Multicentre, open-label, single arm, phase III study of one year duration. Methods. Patients or their caregivers administered up to three doses of rFVIIa (90 μg/kg i.v.) at 3 h intervals within 8 h of the onset of a mild to moderate bleeding episode. Once the subject considered that rFVIIa had been 'effective' with regard to haemostasis (after 1-3 injections), one further imaintenance) dose of rFVIIa was administered. Results. Of 60 patients enrolled, 56 experienced at least one bleed, and 46 completed the one year study. 614 of 877 bleeds (70%) were evaluable according to protocol definitions. Haemostasis was rated as 'effective' in 92% (566/614) of evaluable bleeds after a mean of 2.2 injections. For successfully treated episodes, the time from onset of bleeding until administration of the first injection was 1.1 ± 2.0 h (mean ± SD). Twenty-four hours after initial successful response, haemostasis was reported as having been maintained in 95% of cases. Efficacy was comparable for muscle, joint and target joint, and mucocutaneous bleeding episodes. In an intent-to-treat analysis of all 877 bleeding events, efficacy outcomes were equivalent to the evaluable bleeds, with an effective response in 88% of treated episodes. Treatment-related adverse events occurred in 32 (3% of all) bleeding episodes and consisted of re-bleeds/new bleeds in more than 50% (18/32) of these events. A single episode of superficial thrombophlebitis was the only thrombotic complication encountered, and there were no patient withdrawals due to adverse events. Development of FVII(a) antibodies could not be detected, and hypersensirivity reactions to rFVIIa were not reported. Conclusion. rFVIIa is effective and well tolerated when used in the home setting to treat mild to moderate bleeding episodes in patients with haemophilia A or B with inhibitors.
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