Ypma Paula F, van der Meer Pieter F, Heddle Nancy M, van Hilten Joost A, Stijnen Theo, Middelburg Rutger A, Hervig Tor, van der Bom Johanna G, Brand Anneke, Kerkhoffs Jean-Louis H
Department of Hematology, HAGA Teaching Hospital Den Haag, The Netherlands Center for Clinical Transfusion Research, Sanquin Research, Leiden, The Netherlands.
Center for Clinical Transfusion Research, Sanquin Research, Leiden, The Netherlands.
BMJ Open. 2016 Jan 27;6(1):e010156. doi: 10.1136/bmjopen-2015-010156.
Patients with chemotherapy-induced thrombocytopaenia frequently experience minor and sometimes severe bleeding complications. Unrestrictive availability of safe and effective blood products is presumed by treating physicians as well as patients. Pathogen reduction technology potentially offers the opportunity to enhance safety by reducing bacterial and viral contamination of platelet products along with a potential reduction of alloimmunisation in patients receiving multiple platelet transfusions.
To test efficacy, a randomised, single-blinded, multicentre controlled trial was designed to evaluate clinical non-inferiority of pathogen-reduced platelet concentrates treated by the Mirasol system, compared with standard plasma-stored platelet concentrates using the percentage of patients with WHO grade ≥ 2 bleeding complications as the primary endpoint. The upper limit of the 95% CI of the non-inferiority margin was chosen to be a ≤ 12.5% increase in this percentage. Bleeding symptoms are actively monitored on a daily basis. The adjudication of the bleeding grade is performed by 3 adjudicators, blinded to the platelet product randomisation as well as by an automated computer algorithm. Interim analyses evaluating bleeding complications as well as serious adverse events are performed after each batch of 60 patients. The study started in 2010 and patients will be enrolled up to a maximum of 618 patients, depending on the results of consecutive interim analyses. A flexible stopping rule was designed allowing stopping for non-inferiority or futility. Besides analysing effects of pathogen reduction on clinical efficacy, the Pathogen Reduction Evaluation and Predictive Analytical Rating Score (PREPAReS) is designed to answer several other pending questions and translational issues related to bleeding and alloimmunisation, formulated as secondary and tertiary endpoints.
Ethics approval was obtained in all 3 participating countries. Results of the main trial and each of the secondary endpoints will be submitted for publication in a peer-reviewed journal.
NTR2106; Pre-results.
化疗所致血小板减少症患者经常出现轻微出血并发症，有时甚至是严重出血并发症。治疗医生和患者都认为安全有效的血液制品应随时可用。病原体灭活技术有可能通过减少血小板制品的细菌和病毒污染来提高安全性，同时还可能减少接受多次血小板输注患者的同种免疫反应。
为测试疗效，设计了一项随机、单盲、多中心对照试验，以评估经Mirasol系统处理的病原体灭活血小板浓缩物与标准血浆储存血小板浓缩物相比的临床非劣效性，将世界卫生组织（WHO）≥2级出血并发症患者的百分比作为主要终点。非劣效性界值的95%置信区间上限设定为此百分比增加≤12.5%。每天积极监测出血症状。出血分级由3名裁决者判定，他们对血小板制品随机分组情况不知情，同时还通过自动计算机算法进行判定。每60名患者一批后，进行评估出血并发症以及严重不良事件的中期分析。该研究于2010年开始，根据连续中期分析结果，最多将纳入618名患者。设计了灵活的终止规则，允许因非劣效性或无效性而终止试验。除了分析病原体灭活对临床疗效的影响外，病原体灭活评估与预测分析评分系统（PREPAReS）旨在回答其他几个与出血和同种免疫相关的待解决问题及转化问题，这些问题被设定为次要和三级终点指标。
所有3个参与国都获得了伦理批准。主要试验结果以及每个次要终点指标的结果将提交至同行评审期刊发表。
NTR2106；预结果。
