A prospective randomized trial of high and standard dosages of recombinant factor VIIa for treatment of hemarthroses in hemophiliacs with inhibitors

Aim: A multicenter randomized open-label crossover prospective trial was designed to compare the efficacy, safety, and cost of std. and high dosages of recombinant factor VIIa (rFVIIa) for home treatment of hemarthroses in hemophiliacs with inhibitors. Methods: Patients were instructed to treat, within 6 h from the onset of bleeding, four consecutive hemarthroses of ankles, knees, or elbows, either with the rFVIIa std. dose of 90 mg kg-1 (repeated as necessary every 3 h) or with a single high dose of 270 mg kg-1. Patients who did not achieve a clin. success within 9 h continued rFVIIa treatment with repeated std. doses. Response to treatment was assessed for up to 48 h by patients/caregivers, who reported on a Visual Analog Scale (VAS) graded from 0 to 100 the improvement in symptoms and also rated the responses as effective, partially effective or ineffective. Success was defined a treatment course rated as effective and with a VAS score &rt;=70 and failure a treatment course rated as ineffective and VAS score ?30, whereas treatment courses that did not fulfill these criteria were considered partial responses. Results: Twenty hemophiliacs with inhibitors were originally enrolled (median age: 27 years), 18 of them treated 32 hemarthroses assigned to the std.-dosage and 36 to the high-dosage regimen, during the study period of 18 mo. Forty-eight hemarthroses (71%) occurred in target joints. Success rates for std.- and high-dosage regimens were similar: 31% and 25% at 9 h, 53% and 50% at 24 h, 66% and 64% at 48 h, the end point for outcome assessment. The median no. of rFVIIa infusions needed to achieve a successful course was significantly greater for the std.-dosage (n= 3) than for the high-dosage regimen (n= 1), and the median amt. of rFVIIa ultimately used per successful course was identical (270 mg kg-1). Conclusion: Our results indicate that a high-dosage regimen with rFVIIa for home treatment of hemarthroses is effective, safe, does not imply an increased consumption of rFVIIa and requires the infusion of a smaller no. of rFVIIa doses. Its convenience is particularly relevant in cases with difficult venous access and in hemorrhages into target joints.