title: A randomized comparison of bypassing agents in hemophilia complicated by an inhibitor: the FEIBA NovoSeven Comparative (FENOC) Study.
abstract: The development of inhibitory antibodies to factor VIII is a serious complication of hemophilia. FEIBA (factor VIII inhibitor-bypassing activity), an activated prothrombin complex concentrate (aPCC), and NovoSeven, recombinant factor VIIa (rFVIIa), are used as hemostatic bypassing agents in treating patients with inhibitors. The FENOC study 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 more than 15% was determined to be a clinically acceptable magnitude for equivalence of the 2 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 2 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=.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. This trial was registered at www.clinicaltrials.gov as #NCT00166309.
authors.affiliation: Department for Hematology and Coagulation Disorders, Malmö University Hospital SE-205 02 Malmö, Sweden. jan.astermark@med.lu.se
authors.forename: Jan
authors.initials: J
authors.lastname: Astermark
authors.forename: Sharyne M
authors.initials: SM
authors.lastname: Donfield
authors.forename: Donna M
authors.initials: DM
authors.lastname: DiMichele
authors.forename: Alessandro
authors.initials: A
authors.lastname: Gringeri
authors.forename: Steven A
authors.initials: SA
authors.lastname: Gilbert
authors.forename: Jennifer
authors.initials: J
authors.lastname: Waters
authors.forename: Erik
authors.initials: E
authors.lastname: Berntorp
mesh_terms: D000293:Adolescent; D000328:Adult; D000906:Antibodies / Q000097:blood; D001779:Blood Coagulation Factors / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D015331:Cohort Studies; D018592:Cross-Over Studies; D005167:Factor VII / Q000009:adverse effects / Q000627:therapeutic use*; D005169:Factor VIII / Q000037:antagonists & inhibitors / Q000276:immunology; D015942:Factor VIIa; D006467:Hemophilia A / Q000150:complications* / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D008875:Middle Aged; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000906:Antibodies; D001779:Blood Coagulation Factors; D011994:Recombinant Proteins; C025667:prothrombin complex concentrates; D005167:Factor VII; D005169:Factor VIII; C103587:recombinant FVIIa; D015942:Factor VIIa