DETERMINATION OF OPTIMAL PROPHYLACTIC PLATELET DOSE STRATEGY TO PRVNT BLEEDING

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。方案概述：随着血小板的使用继续以不成比例的高于红细胞的速度增加，确定最具成本效益的血小板支持策略非常重要。确定和实施最安全和最具成本效益的血小板支持策略对于在不耗尽血小板供应的情况下进行有效的疾病管理至关重要。在医生的控制范围内，对血小板输注总量有显著影响的两个最重要因素是：1)选择输注预防性血小板输注触发器；2)每次输血的血小板数量。在过去的15年里，关于血小板输注触发的临床数据提供了丰富的信息。每次输血血小板的最佳数量仍然是一个极具争议的话题。迄今为止，尚未进行前瞻性血小板输注试验，在该试验中，患者在血小板减少期间随机分配指定的血小板剂量，以评估不同剂量对输注结果的影响。血小板治疗的不同剂量策略可能存在安全性问题。与低剂量治疗相比，高剂量血小板输注治疗在更大比例的时间内维持较高的血小板计数可能提供更好的止血效果。另一方面，触发性研究数据表明，只要维持5000个血小板的基线水平，就不存在血小板输注剂量与血液统计学相关的安全性问题。本研究将探讨三种不同给药策略对与干细胞移植或化疗相关的血小板减少住院患者的安全性。主要终点是每个治疗组中至少有一天发生2级或以上出血的患者百分比。获取成本和安全性关键数据的最重要次要终点是分配的血小板总数、输血事件总数、最高出血等级和出血严重程度评分（如果该评分在血小板剂量试验结束时得到验证和公布，并且收集了计算该评分所需的信息）。这项试验的结果可能对标准的医疗实践产生重大影响。血小板剂量试验是一项多地点试验，将在美国招募1350名患者。患者将根据体表面积（BSA）被随机分配到三个血小板输注治疗组：低剂量：1.1 x 1011/m2（中剂量）中剂量：2.2 x 1011/m2高剂量：4.4 x 1011/m2（中剂量的两倍）可接受的剂量是在目标剂量以上或以下25%范围内的剂量。对于晨间血小板计数<10,000/ul的患者，将按指定剂量预防性输注。如果输血后血小板计数不<10,000/ul，医生将被允许再次输血血小板，但不是必须这样做。该方案允许在侵入性手术或活动性出血的情况下增加血小板。研究人员将每天通过对患者的身体评估、患者访谈以及患者病历和实验室数据的审查来评估出血情况。出血等级的实际分配将在数据协调中心进行，通过计算机化算法对病例报告表格中的数据进行评估，并判定因出血死亡。输血医学/止血网络新英格兰研究机构。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. PROTOCOL SYNOPSIS As platelet use continues to increase at a rate disproportionately higher than that of red cells, it is important to identify the most cost-effective strategies for providing platelet support. Identification and implementation of the most safe and cost effective strategies for providing platelet support is crucial for effective disease management without depleting platelet supplies. The two most important factors within the control of the ordering physician that will significantly influence the total amount of platelets transfused are: 1) the prophylactic platelet transfusion trigger selected for transfusion; and 2) the number of platelets given per transfusion. Informative clinical data have been provided in the last fifteen years concerning the platelet transfusion trigger. The optimal quantity of platelets to be used per transfusion remains a highly controversial subject. To date, no prospective platelet transfusion trials have been performed in which patients are randomized to an assigned platelet dose throughout their period of thrombocytopenia to evaluate the effects of different doses on transfusion outcomes. There may be safety issues associated with different dosing strategies for platelet therapy. Maintaining a higher platelet count for a greater percentage of the time with higher dose platelet transfusion therapy might provide better hemostasis than lower dose therapy. On the other hand, trigger study data suggest that there may be no hemostatistically-related safety issues based on the dose of platelets transfused as long as a baseline level of > 5,000 platelets is maintained. This study will investigate the safety of three different dosing strategies for inpatients with thrombocytopenia related to stem cell transplants or chemotherapy. The primary endpoint is the percentage of patients in each treatment arm who have at least one day with Grade 2 or higher bleeding. The most important secondary endpoints, capturing key data on costs and safety, are the total number of platelets dispensed, the total number of transfusion events, the highest grade of bleeding, and the bleeding severity score (if such a score has been validated and published by the end of the Platelet Dose trial, and the necessary information to calculate the score was collected). The results of this trial could have a major effect on standard medical practice. The Platelet Dose Trial is a multi-site trial that will enroll 1350 patients in the United States. Patients will be randomized with equal allocation to three platelet transfusion therapy groups based on body surface area (BSA): Lower dose: 1.1 x 1011/m2 (¿¿¿¿ of the medium dose) Medium dose: 2.2 x 1011/m2 Higher dose: 4.4 x 1011/m2 (twice the medium dose) An acceptable dose will be a dose that is within a range of 25% either above or below the target dose. Patients will be prophylactically transfused at their assigned dose for morning platelet counts of <10,000/ul. If the post-transfusion platelet count is not <10,000/ul the physician will be allowed to order another platelet transfusion but is not required to do so. The protocol allows for additional platelets in the case of invasive procedures or active bleeding. Assessment of bleeding by study personnel will be performed daily by means of physical assessment of the patient, patient interview and review of patient chart and laboratory data. The actual assignment of the bleeding grades will occur at the Data Coordinating Center by a computerized algorithm programmed to evaluate the data from the case report forms, plus adjudication of death due to bleeding. Transfusion Medicine/Hemostasis Network New England Research Institutes, Inc.