Is pharmacokinetic-guided dosing of desmopressin and von Willebrand factor-containing concentrates in individuals with von Willebrand disease or low von Willebrand factor reliable and feasible? A protocol for a multicentre, non-randomised, open label cohort trial, the OPTI-CLOT: to WiN study. Issue 2 (15th February 2022)

• Record Type: Journal Article
• Authors: Heijdra, Jessica M; Al Arashi, Wala; de Jager, Nico C B; Cloesmeijer, Michael E; Bukkems, Laura H; Zwaan, Christian M; Leebeek, Frank W G; Mathôt, Ron A A; Cnossen, Marjon H
• Other Names: author non-byline.; Cnossen MH author non-byline.; Leebeek FWG author non-byline.; Fijnvandraat K author non-byline.; Mathôt RAA author non-byline.; Meijer K author non-byline.; Kruip MJHA author non-byline.; Polinder S author non-byline.; Coppens M author non-byline.; Tamminga RYJ author non-byline.; Meijer K author non-byline.; Laros-van Gorkom BAP author non-byline.; Brons P author non-byline.; Schols SEM author non-byline.; van der Meer FJM author non-byline.; Eikenboom HCJ author non-byline.; Schutgens REG author non-byline.; Fischer K author non-byline.; Heubel-Moenen F author non-byline.; Nieuwenhuizen L author non-byline.; Ypma P author non-byline.; Driessens MHE author non-byline.; Zwaan CM author non-byline.; van Vliet I author non-byline.; Collins PW author non-byline.; Liesner R author non-byline.; Chowdary P author non-byline.; Keeling D author non-byline.; Lock J author non-byline.; Hazendonk HCAM author non-byline.; van Moort I author non-byline.; Preijers T author non-byline.; Heijdra JM author non-byline.; de Jager NCB author non-byline.; Goedhart MCHJ author non-byline.; Bukkems LH author non-byline.; Al Arashi W author non-byline.; Cloesmeijer ME author non-byline.; Janssen A author non-byline.;
• Is Part Of: BMJ open. Volume 12:Issue 2(2022)
• Publication Date: 2022-02-15
• Subjects: bleeding disorders & coagulopathies -- protocols & guidelines -- clinical trials; Medicine -- Research -- Periodicals; 610.72
• DOI: 10.1136/bmjopen-2021-049493
• Languages: English
• ISSNs: 2044-6055

Abstract

Abstract : Introduction: Von Willebrand disease (VWD) is a bleeding disorder, caused by a deficiency or defect of von Willebrand factor (VWF). In case of medical procedures or bleeding, patients are treated with desmopressin and/or VWF-containing concentrates to increase plasma VWF and factor VIII (FVIII). However, in many cases these factor levels are outside the targeted range. Therefore, population pharmacokinetic (PK) models have been developed, which aim to quantify and explain intraindividual and interindividual differences in treatment response. These models enable calculation of individual PK parameters by Bayesian analysis, based on an individual desmopressin test or PK profile with a VWF-containing concentrate. Subsequently, the dose necessary for an individual to achieve coagulation factor target levels can be calculated. Methods and analysis: Primary aim of this study is to assess the predictive performance (the difference between predicted and measured von VWF activity and FVIII levels) of Bayesian forecasting using the developed population PK models in four different situations: (A) desmopressin testing (n≥30); (B) medical procedures (n=70; 30 receiving desmopressin, 30 receiving VWF-containing concentrate and 10 receiving a combination of both); (C) bleeding episodes (n=20; 10 receiving desmopressin and 10 receiving VWF-containing concentrate) and (D) prophylaxis with a VWF-containing concentrate (n=3 to 5). Individuals with all types of VWD and individuals with low VWF (VWF 0.30–0.60 IU/mL) will be included. Reliability and feasibility of PK-guided dosing will be tested by assessing predictive performance, treatment duration, haemostasis, patient satisfaction and physician satisfaction. Ethics and dissemination: The OPTI-CLOT:to WiN study was approved by the medical ethics committee of the Erasmus MC, University Medical Centre Rotterdam, the Netherlands. Results of the study will be communicated through publication in international scientific journals and presentation at (inter)national conferences. Trial registration number: NL7212 (NTR7411); Pre-results, EudraCT 2018-001631-46.