Hazendonk Hendrika C A M, van Moort Iris, Fijnvandraat Karin, Kruip Marieke J H A, Laros-van Gorkom Britta A P, van der Meer Felix J M, Meijer Karina, Peters Marjolein, Schutgens Roger E G, Zwaan Christian M, Driessens Mariette H E, Polinder Suzanne, Leebeek Frank W G, Mathôt Ron A A, Cnossen Marjon H
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:
Thromb Haemost. 2015 Aug 31;114(3):639-44. doi: 10.1160/TH14-11-0925. Epub 2015 Jun 11.
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.
甲型血友病是一种X连锁遗传性罕见出血性疾病，由凝血因子VIII（FVIII）缺乏引起。先前关于预防性给药的研究表明，通过基于个体药代动力学（PK）分析和群体PK数据的联合分析（贝叶斯分析）来个体化给药，可以显著降低FVIII的消耗量。到目前为止，尚未有研究使用基于PK群体模型的迭代PK引导给药来探讨围手术期浓缩物的消耗量。“OPTI-CLOT”试验是一项开放标签、前瞻性、多中心随机对照优势试验（RCT），旨在检测与标准给药程序相比，采用迭代贝叶斯PK引导给药时围手术期FVIII浓缩物消耗量有25%的差异。将纳入60名年龄≥12岁、FVIII血浆水平≤0.05 IU/ml(-1)的甲型血友病患者，这些患者因择期、低或中度风险手术需要通过持续或推注输注进行FVIII替代治疗。拟开展的研究旨在基于最近构建的围手术期PK群体模型，研究一种新型的围手术期迭代PK引导给药策略。该模型可能会减少凝血因子浓缩物的给药不足和给药过量，预计总体上可将FVIII消耗量至少降低25%。此外，参与研究的医院将积累PK引导给药的经验，促进该干预措施未来的实施，有望优化当前的治疗并降低治疗成本。
