DETERMINATION OF OPTIMAL PROPHYLACTIC PLATELET DOSE STRATEGY TO PRVNT BLEEDING

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 由于血小板的使用继续以不成比例地高于红细胞的速度增加，因此确定提供血小板支持的最具成本效益的策略非常重要。 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有效的疾病管理而不消耗血小板供应至关重要。处方医生控制范围内的两个最重要的因素将显著影响血小板输注总量：1）选择用于输注的预防性血小板输注触发因素; 2）每次输注的血小板数量。 在过去15年中提供了关于血小板输注触发因素的信息性临床数据。每次输血的最佳血小板量仍然是一个非常有争议的问题。迄今为止，尚未进行前瞻性血小板输注试验，其中患者在血小板减少症期间随机分配至指定的血小板剂量，以评价不同剂量对输注结局的影响。 血小板治疗的不同给药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的时间百分比内维持更高的血小板计数可能提供更好的止血效果。另一方面，触发研究数据表明，只要维持> 5，000个血小板的基线水平，基于输注的血小板剂量，就可能不存在与造血相关的安全性问题。 本研究将研究三种不同给药策略治疗与干细胞移植或化疗相关的血小板减少症住院患者的安全性。主要终点是每个治疗组中至少有一天发生2级或2级以上出血的患者百分比。最重要的次要终点（获取有关成本和安全性的关键数据）是分发的血小板总数、输血事件总数、最高级别的出血和出血严重程度评分（如果在血小板剂量试验结束时已验证并公布了此类评分，并且收集了计算评分的必要信息）。这项试验的结果可能会对标准医疗实践产生重大影响。 血小板剂量试验是一项多中心试验，将在美国招募1350名患者。 根据体表面积（BSA），患者将被随机平均分配至3个血小板输注治疗组：较低剂量：1.1 x 1011/m2（中剂量的1/2）中剂量：2.2 x 1011/m2高剂量：4.4 x 1011/m2（中等剂量的两倍）可接受剂量是在目标剂量以上或以下25%范围内的剂量。对于早晨血小板计数<10，000/ul的患者，将以其分配的剂量进行辅助输血。如果输注后血小板计数不<10，000/ul，医生将被允许再次输注血小板，但不要求这样做。该方案允许在侵入性手术或活动性出血的情况下额外输注血小板。 研究工作人员将通过患者体格评估、患者访谈以及患者病历和实验室数据审查，每天进行出血评估。出血等级的实际分配将在数据协调中心通过编程的计算机化算法进行，以评价病例报告表中的数据，以及出血所致死亡的裁定。输血医学/止血网络新英格兰研究所公司

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/m2Higher 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.