2003; baxter - Supplements - Haematologica

[General Treatment of Bleeding Episodes]review paperThe Feiba NovoSevenComparative Study (FENOC)haematologica 2003; 88(suppl. n. 12):26-28http://www.haematologica.org/free/immunotolerance2001.pdfERIK BERNTORP, JAN ASTERMARKDepartment of Coagulation Disorders, Malmö UniversityHospital, Malmö, SwedenThe development of an inhibitor is still the mainthreat to the health of hemophiliacs. By-passingagents, such as activated prothrombin complex concentrateand recombinant factor VIIa, are widelyused to treat acute hemorrhages in hemophilia Ainhibitor patients. The efficacy of these productsvaries among patients and the treatment is expensive.In the Feiba NovoSeven Comparative Study(FENOC) a comparison is made between the activatedprothrombin complex concentrate Feiba andrecombinant factor VIIa NovoSeven. The study is aprospective, randomized, multi-center study, inwhich two bleeds in each of 60 patients will be randomizedand treated with the products. The primaryend-point is evaluation of the hemostatic effect at6 hours. Dose and dose interval will be as recommendedby the manufacturers. Using an in vitrothrombin generation test, an attempt to predict efficacyof the product will be made. The FENOC studyshould be considered as a basic study in order togain more knowledge about by-passing agents andhas the potential to create a platform for future studieson the treatment of acute bleeds in inhibitorpatients.Correspondence: Erik Berntorp, Department of CoagulationDisorders, Malmö University Hospital, SE-205 02 Malmö,Sweden. Phone: international +46.40.332392.Fax: international +46.40.336255.E-mail: erik.berntorp@medforsk.mas.lu.seThe incidence of inhibitors in patients withsevere hemophilia A is around 30% inrecent prospective studies, 1-3 although arange from zero up to 52% has been reported. 4,5There are two main options in the treatment ofan inhibitor patient, the main goal being to renderthe patient tolerant to replacement therapywith factor VIII by induction of immune tolerance.The other option, which can also be usedduring immune tolerance induction before thetolerated state has been achieved, is to treat acutehemorrhages using by-passing agents, which tosome extent improve hemostasis. Among theseagents, the activated prothrombin complex concentrateFeiba has been widely used for manyyears. 6,7 More recently, recombinant factor VIIa(NovoSeven) has been added to the therapeuticarmamentarium. 8,9 Both these products havebeen found to be effective in up to 80-90% of allhemorrhages in non-randomized studies. Theexact by-passing hemostatic mechanism(s) foreach product is not fully understood and thedosing also needs to be further explored. Thenumber of injections given for a bleed hasranged greatly in different reports and it isunknown so far whether one of the productsmight have a better effect in certain patients.Treatment with by-passing agents is costly.Therefore, it is important to perform controlledstudies with these products. As yet, a comparativein vivo study of effect as well as cost-efficacyis lacking. The FENOC study is designed toassess the hemostatic effects of Feiba and Novo-Seven in a randomized, controlled study. Thestudy is multi-center, multi-national and is organizedfrom Malmö with the authors as principalinvestigators. Additional principal investigatorshave been appointed for Italy (AlessandroGringeri, Milan) and North America (Donna DiMichele, New York City, USA).Study materialSixty patients with congenital hemophilia Awith an inhibitor and the need for by-passingagents in the case of joint bleeds will be recruited.The expected bleeding frequency is at leastthree joint bleeds per year. The lower limit of agefor eligibility is two years. Exclusion criteria areother congenital and acquired bleeding disorders,symptomatic liver disease with an INR >1.5haematologica vol. 88(supplement n. 12):september 2003