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Thromb Haemost 2015; 114(03): 639-644
DOI: 10.1160/TH14-11-0925
Trial Protocol Design Paper
Schattauer GmbH

The “OPTI-CLOT” trial[*]

A randomised controlled trial on periOperative PharmacokineTIc-guided dosing of CLOTting factor concentrate in haemophilia A
Hendrika C. A. M. Hazendonk
1   Department of Paediatric Haematology, Erasmus University Medical Centre-Sophia Children’s Hospital Rotterdam, Rotterdam, The Netherlands
,
Iris van Moort
1   Department of Paediatric Haematology, Erasmus University Medical Centre-Sophia Children’s Hospital Rotterdam, Rotterdam, The Netherlands
,
Karin Fijnvandraat
2   Department of Paediatric Haematology, Academic Medical Centre Amsterdam, Amsterdam, The Netherlands
,
Marieke J. H. A. Kruip
3   Department of Haematology, Erasmus University Medical Centre Rotterdam, Rotterdam, The Netherlands
,
Britta A. P. Laros-van Gorkom
4   Department of Haematology, Radboud university medical centre, Nijmegen, The Netherlands
,
Felix J. M. van der Meer
5   Department of Thrombosis and Haemostasis, Leiden University Medical Centre, Leiden, The Netherlands
,
Karina Meijer
6   Department of Haematology, University Medical Centre Groningen, Groningen, The Netherlands
,
Marjolein Peters
2   Department of Paediatric Haematology, Academic Medical Centre Amsterdam, Amsterdam, The Netherlands
,
Roger E. G. Schutgens
7   Department of Haematology, University Medical Centre Utrecht, Utrecht, The Netherlands
,
Christian M. Zwaan
8   Department of Paediatric Oncology, Erasmus University Medical Centre-Sophia Children’s Hospital Rotterdam, Rotterdam, The Netherlands
,
Mariette H. E. Driessens
9   Netherlands Haemophilia Patient Society, Nijkerk, The Netherlands
,
Suzanne Polinder
10   Department of Public Health, Erasmus University Medical Centre Rotterdam, Rotterdam, The Netherlands
,
Frank W. G. Leebeek
3   Department of Haematology, Erasmus University Medical Centre Rotterdam, Rotterdam, The Netherlands
,
Ron A. A. Mathôt
11   Department of Hospital Pharmacy-Clinical Pharmacology, Academic Medical Centre Amsterdam, Amsterdam, The Netherlands
,
Marjon H. Cnossen
1   Department of Paediatric Haematology, Erasmus University Medical Centre-Sophia Children’s Hospital Rotterdam, Rotterdam, The Netherlands
› Author Affiliations
Further Information

Publication History

Received: 10 November 2014

Accepted after major revision: 28 March 2015

Publication Date:
01 December 2017 (online)

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Summary

Haemophilia A is an X-linked inherited, rare bleeding disorder, caused by a deficiency of coagulation factor VIII (FVIII). Previous studies in prophylactic dosing have demonstrated that FVIII consumption can be significantly reduced by individualising dosing based on combined analysis of individual pharmacokinetic (PK) profiling and population PK data (Bayesian analysis). So far, no studies have been performed that address perioperative concentrate consumption using iterative PK-guided dosing based on a PK population model. The “OPTI-CLOT” trial is an open-label, prospective, multicentre randomised controlled superiority trial (RCT), aiming to detect a 25 % difference in perioperative FVIII concentrate consumption with iterative Bayesian PK-guided dosing in comparison to the standard dosing procedure. Sixty haemophilia A patients ≥ 12 years of age, with FVIII plasma levels ≤0.05 IUml-1 will be included requiring FVIII replacement therapy administered either by continuous or bolus infusion for an elective, low or medium risk surgical procedure. The proposed study aims to investigate a novel perioperative iterative PK-guided dosing strategy, based on a recently constructed perioperative PK population model. This model will potentially decrease underdosing and overdosing of clotting factor concentrate and is expected to overall reduce FVIII consumption by minimally 25 %. Moreover, participating hospitals will gain experience with PK-guided dosing, facilitating future implementation of this intervention which is expected to optimise current care and reduce costs of treatment.

This study is part of the “OPTI-CLOT” research programme (Patient tailOred PharmacokineTIc-guided dosing of CLOTting factor concentrates in clotting disorders)”, an (inter)national multicentre study aiming to implement PKguided dosing of clotting factor replacement therapy by initiating studies to demonstrate its implications and feasibility, improve PK models and to increase knowledge of patient-tailored PK-guided dosing.

Keywords

Haemophilia therapy - factor VIII - factor concentrates - pharmacokinetics - Bayesian analysis

* Trial registration: NTR4121.


 

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