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 e.cacy, safety, and cost of standard and high dosages of recombinant factor VIIa (rFVIIa) for home treatment of hemarthroses in hemophiliacs with inhibitors. Methods: Patients were in structed to treat, within 6h from the onset of bleeding, four consecutive hemarthroses of ankles, knees, or elbows, either with the rFVIIa standard dose of 90 μg kg ^-1) (repeated as necessary every 3 h) or with a single high dose of 270 μg kg ^-1). Patients who did not achieve a clinical success within 9 h continued rFVIIa treatment with repeated standard doses. Response to treatment was assessed for up to 48 h by patients/ caregivers, who reported on a Visual Analogue Scale (VAS) graded from 0 to 100 the improvement in symptoms and also rated the responses as effective, partially effective or ineffective. Success was de.ned a treatment course rated as effective and with a VAS score ≥70 and failure a treatment course rated as ine.ective 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 standard-dosage and 36 to the high-dosage regimen, during the study period of 18 months. Forty-eight hemarthroses (71%) occurred in target joints. Success rates for standard- 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 number of rFVIIa infusions needed to achieve a successful course was signi.cantly greater for the standard-dosage (n - 3) than for the high-dosage regimen (n = 1), and the median amount of rFVIIa ultimately used per successful course was identical (270 μg 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 number of rFVIIa doses. Its convenience is particularly relevant in cases with difficult venous access and in hemorrhages into target joints.