Design of a Prospective Study on Pharmacokinetic-Guided Dosing of Prophylactic Factor Replacement in Hemophilia A and B (OPTI-CLOT TARGET Study)

Abstract

In resource-rich countries, almost all severe hemophilia patients receive prophylactic replacement therapy with factor concentrates to prevent spontaneous bleeding in joints and muscles to decrease the development of arthropathy and risk of long-term disability. Pharmacokinetic (PK)-guided dosing can be applied to individualize factor replacement therapy, as interindividual differences in PK parameters influence factor VIII (FVIII) and FIX activity levels. PK-guided dosing may therefore lead to more optimal safeguarding of FVIII/FIX levels during prophylaxis and on demand treatment. The OPTI-CLOT TARGET study is a multicenter, nonrandomized, prospective cohort study that aims to investigate the reliability and feasibility of PK-guided prophylactic dosing of factor concentrates in hemophilia-A and -B patients in daily clinical practice. At least 50 patients of all ages on prophylactic treatment using standard half-life (SHL) and extended half-life (EHL) factor concentrates will be included during 9 months and will receive PK-guided treatment. As primary endpoint, a minimum of four FVIII/FIX levels will be compared with FVIII/FIX levels as predicted by Bayesian forecasting. Secondary endpoints are the association of FVIII and FIX levels with bleeding episodes and physical activity, expectations and experiences, economic analyses, and optimization of population PK models. This study will lead to more insight in the reliability and feasibility of PK-guided dosing in hemophilia patients. Moreover, it will contribute to personalization of treatment by greater knowledge of dosing regimens needed to prevent and treat bleeding in the individual patient and provide evidence to more clearly associate factor activity levels with bleeding risk.