Design of a Prospective Study on Pharmacokinetic-Guided Dosing of Prophylactic Factor Replacement in Hemophilia A and B (OPTI-CLOT TARGET Study)
Tine M.H.J. Goedhart,
Laura H. Bukkems,
Michiel Coppens,
Karin J. Fijnvandraat,
Saskia E.M. Schols,
Roger E.G. Schutgens,
Jeroen Eikenboom,
Floor C.J.I. Heubel-Moenen,
Paula F. Ypma,
L. Nieuwenhuizen,
K. Meijer,
Frank W. G. Leebeek,
Ron A.A. Mathôt,
Marjon H. Cnossen
Affiliations
Tine M.H.J. Goedhart
Department of Pediatric Hematology and Oncology, Erasmus MC Sophia Children's Hospital, University Medical Center Rotterdam, Rotterdam, The Netherlands
Laura H. Bukkems
Department of Clinical Pharmacology - Hospital Pharmacy, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
Michiel Coppens
Department of Vascular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
Karin J. Fijnvandraat
Department of Pediatric Hematology, Amsterdam UMC, Emma Children's Hospital, University of Amsterdam, Meibergdreef 9, Amsterdam, the Netherlands
Saskia E.M. Schols
Department of Hematology, Radboud University Medical Center, Nijmegen, and the Hemophilia Treatment Center Nijmegen-Eindhoven-Maastricht, The Netherlands
Roger E.G. Schutgens
Van Creveldkliniek, University Medical Center Utrecht, Utrecht, The Netherlands
Jeroen Eikenboom
Department of Internal Medicine, Division of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands
Floor C.J.I. Heubel-Moenen
Department of Hematology, Maastricht University Medical Center, Maastricht, The Netherlands
Paula F. Ypma
Department of Hematology, Haga Hospital, The Hague, The Netherlands
L. Nieuwenhuizen
Department of Internal Medicine, Maxima Medical Center, Veldhoven, The Netherlands
K. Meijer
Department of Hematology, University Medical Center Groningen, Groningen, The Netherlands
Frank W. G. Leebeek
Department of Hematology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
Ron A.A. Mathôt
Department of Clinical Pharmacology - Hospital Pharmacy, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
Marjon H. Cnossen
Department of Pediatric Hematology and Oncology, Erasmus MC Sophia Children's Hospital, University Medical Center Rotterdam, Rotterdam, The Netherlands
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.
