title: The "OPTI-CLOT" trial. A randomised controlled trial on periOperative PharmacokineTIc-guided dosing of CLOTting factor concentrate in haemophilia A.
abstract: 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.
authors.forename: Hendrika C A M
authors.initials: HC
authors.lastname: Hazendonk
authors.forename: Iris
authors.initials: I
authors.lastname: van Moort
authors.forename: Karin
authors.initials: K
authors.lastname: Fijnvandraat
authors.forename: Marieke J H A
authors.initials: MJ
authors.lastname: Kruip
authors.forename: Britta A P
authors.initials: BA
authors.lastname: Laros-van Gorkom
authors.forename: Felix J M
authors.initials: FJ
authors.lastname: van der Meer
authors.forename: Karina
authors.initials: K
authors.lastname: Meijer
authors.forename: Marjolein
authors.initials: M
authors.lastname: Peters
authors.forename: Roger E G
authors.initials: RE
authors.lastname: Schutgens
authors.forename: Christian M
authors.initials: CM
authors.lastname: Zwaan
authors.forename: Mariette H E
authors.initials: MH
authors.lastname: Driessens
authors.forename: Suzanne
authors.initials: S
authors.lastname: Polinder
authors.forename: Frank W G
authors.initials: FW
authors.lastname: Leebeek
authors.forename: Ron A A
authors.initials: RA
authors.lastname: Mathôt
authors.affiliation: M. H. Cnossen, MD, PhD, Department of Paediatric Haematology, Erasmus University Medical Centre, Sophia Children's Hospital Rotterdam, P. O. Box 2040, 3000 CA Rotterdam, the Netherlands, E-mail: m.cnossen@erasmusmc.nl.
authors.forename: Marjon H
authors.initials: MH
authors.lastname: Cnossen
mesh_terms: D001499:Bayes Theorem; D002985:Clinical Protocols; D003029:Coagulants / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule; D054796:Drug Dosage Calculations; D017558:Elective Surgical Procedures; D005169:Factor VIII / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D006467:Hemophilia A / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D006487:Hemostasis / Q000187:drug effects*; D006801:Humans; D007262:Infusions, Intravenous; D008954:Models, Biological; D009426:Netherlands; D019990:Perioperative Care; D011446:Prospective Studies; D012107:Research Design; D016896:Treatment Outcome
chemical_list: D003029:Coagulants; C078147:F8 protein, human; D005169:Factor VIII
keywords: Bayesian analysis; Haemophilia therapy; factor VIII; factor concentrates; pharmacokinetics