Submitted April 20, 2006
Accepted September 4, 2006
A randomized comparison of bypassing agents in hemophilia complicated by an inhibitor
Jan Astermark*, Sharyne M. Donfield, Donna M. DiMichele, Alessandro Gringeri, Steven A. Gilbert, Jennifer Waters, and Erik Berntorp
Department for Coagulation Disorders, Malmo University Hospital, Malmo, Sweden
Department of Biostatistics, Rho, Inc., Chapel Hill, NC
Department of Pediatrics, Weill Medical College, Cornell University, New York, NY
Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, University of Milan, Milan, Italy
* Corresponding author; email: jan.astermark{at}med.lu.se.
The development of inhibitory antibodies to factor VIII is a serious complication of hemophilia. FEIBA® , an activated prothrombin complex concentrate (aPCC) and NovoSeven® , recombinant factor VIIa (rFVIIa), are used as hemostatic bypassing agents in treating patients with inhibitors. FENOC was designed to test equivalence of the products in the treatment of ankle, knee and elbow joint bleeding. A prospective, open-label, randomized, crossover, equivalency design was used. The parameters of interest were the percentage of patients who reported efficacy in response to FEIBA® , and the percentage that reported efficacy in response to NovoSeven® . A difference in these percentages of no greater than 15% was determined to be a clinically acceptable magnitude for equivalence of the two products. The primary outcome was evaluation 6 hours after treatment. Data for 96 bleeding episodes contributed by 48 participants were analyzed. The criterion for declaring the two products equivalent at 6 hours was not met, however, the confidence interval of the difference in percentages of efficacy reported for each product only slightly exceeded the 15% boundary (-11.4%, 15.7%), p=0.059. FEIBA® and NovoSeven® appear to exhibit a similar effect on joint bleeds although the efficacy between products is rated differently by a substantial proportion of patients.
