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CC BY 4.0 · TH Open 2022; 06(01): e60-e69
DOI: 10.1055/a-1760-0105
Original Article

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    *
1   Department of Pediatric Hematology and Oncology, Erasmus MC Sophia Children's Hospital, University Medical Center Rotterdam, Rotterdam, The Netherlands
,
Laura H. Bukkems    *
2   Department of Clinical Pharmacology - Hospital Pharmacy, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
,
Michiel Coppens
3   Department of Vascular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
,
Karin J. Fijnvandraat
4   Department of Pediatric Hematology, Amsterdam UMC, Emma Children's Hospital, University of Amsterdam, Meibergdreef 9, Amsterdam, the Netherlands
,
Saskia E.M. Schols
5   Department of Hematology, Radboud University Medical Center, Nijmegen, and the Hemophilia Treatment Center Nijmegen-Eindhoven-Maastricht, The Netherlands
,
Roger E.G. Schutgens 
6   Van Creveldkliniek, University Medical Center Utrecht, Utrecht, The Netherlands
,
Jeroen Eikenboom
7   Department of Internal Medicine, Division of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands
,
Floor C.J.I. Heubel-Moenen
8   Department of Hematology, Maastricht University Medical Center, Maastricht, The Netherlands
,
Paula F. Ypma
9   Department of Hematology, Haga Hospital, The Hague, The Netherlands
,
L. Nieuwenhuizen
10   Department of Internal Medicine, Maxima Medical Center, Veldhoven, The Netherlands
,
K. Meijer
11   Department of Hematology, University Medical Center Groningen, Groningen, The Netherlands
,
Frank W. G. Leebeek
12   Department of Hematology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
,
Ron A.A. Mathôt   *
2   Department of Clinical Pharmacology - Hospital Pharmacy, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
,
Marjon H. Cnossen   *
1   Department of Pediatric Hematology and Oncology, Erasmus MC Sophia Children's Hospital, University Medical Center Rotterdam, Rotterdam, The Netherlands
› Author Affiliations Funding This study was funded by Innovatiefonds Zorgverzekeraars, grant number: Project 3216; and Nederlandse Organisatie voor Wetenschappelijk Onderzoek, grant number: NWA.1160.18.038.
› Further Information
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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.

Keywords

hemophilia - pharmacokinetics - factor VIII - factor IX - prophylaxis

Note

This study is part of the OPTI-CLOT Research Programme (Patient tailOred PharmacokineTIc-guided dosing of CLOTting factor concentrates and desmopressin in bleeding disorders),” an (inter)national multicenter study aiming to implement pharmacokinetic (PK)-guided dosing of replacement therapy and desmopressin by initiating studies to demonstrate its implications and feasibility, improve PK models, and to increase knowledge of patient-tailored PK-guided dosing which is currently part of the SYMPHONY consortium that aims to unravel the origins of the interindividual variation in bleeding phenotype in order to install personalized treatment in all inherited bleeding disorders.


* Shared first and last authorships.




Publication History

Received: 12 August 2021

Accepted: 11 January 2022

Accepted Manuscript online:
03 February 2022

Article published online:
10 March 2022

© 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).

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