Resuscitation Outcomes Consortium (ROC) Data Coordinating Center

描述(由申请人提供)：复苏结果联盟(ROC)将进行前瞻性、随机化、最佳血小板和血浆比率(PROPPR)第三阶段试验，以比较接受不同血液产品比率的580名受试者的24小时和30天死亡率(共同初级结果)。PROPPR中的受试者必须符合资格标准，并被预测在紧急入院I级成人创伤中心后24小时内接受大量输血(MT)。试验首先在至少四个地点进行先锋阶段(120名受试者)，研究两种比例(1：1：2，1：1：3，血浆：血小板：红细胞)，并选择更好的手臂进行第三阶段的比较，与1：1：1最接近于全血。每只手臂有40名受试者，正确选择更好的手臂的概率为83%。在先锋阶段，我们将评估方案的安全性和可行性，并开始研究创伤引起的凝血障碍(TIC)和炎症标志物。在第三阶段，共有580名受试者(包括80名来自先锋阶段的受试者)提供90%的力量来检测24小时死亡率相差10%或以上，88%的力量来探测30天死亡率相差12%或以上，假设每个阿尔法=0.044，双侧测试，1：1：1组中11%的24小时死亡率和23%的30天死亡率。Mantel-Haenszel检验将使用SITE作为分层变量。我们将描述TIC和炎症的机制驱动因素和后遗症，并描述严重创伤患者严重损伤后复苏的凝血环境的自然历史。考虑到危及生命的情况和每个治疗臂受益的前景，将使用知情同意的例外情况。中华民国数据协调中心(DCC)的Susanne May是Contact的首席调查员(PI)。DCC的Gerald van Belle是PI-PROPPR。John Holcomb是UTHealth临床协调中心的PI，这是我国的一个卫星，负责监督临床站点以及实验室和系统生物学部分。加州大学卫生学院公共卫生学院的Barbara Tilley是我国卫星数据协调中心的PI，管理数据，监督数据质量，提供盲目和非盲目数据的分析，提供现场研究监测，并向数据安全监测委员会报告安全和中期分析。 相关性：从这项第三阶段试验中获得的知识将影响医院大出血患者的输血方式。通过更好地决定哪些患者最需要大量输血，并输注适当比例的血液产品以减轻潜在的创伤性凝血障碍，创伤救援队将有能力影响人群，降低原本可以预防的失血性休克死亡人数。

DESCRIPTION (provided by applicant): The Resuscitation Outcomes Consortium (ROC) will conduct the Prospective, Randomized, Optimal Platelet and Plasma Ratios (PROPPR) Phase III trial to compare 24-hour and 30-day mortality (co-primary outcomes) in 580 subjects receiving differing blood product ratios. Subjects in PROPPR must meet eligibility criteria and be predicted to receive a massive transfusion (MT) within 24 hours of emergency admission to a Level I Adult Trauma Center. The trial begins with a Vanguard Stage (120 subjects) conducted in at least four sites to study two ratios (1:1:2, 1:1:3, plasma:platelets:RBCs) and choose the better arm to carry forward into Phase III to compare to 1:1:1. The closest equivalent to whole blood. 40 subjects per arm, provide 83% probability of correctly choosing the better arm. In the Vanguard Stage, we will assess protocol safety, feasibility and begin study of trauma induced coagulopathy (TIC) and inflammatory markers. In Phase III, 580 total subjects (including 80 from the Vanguard Stage), provide 90% power to detect a difference of 10% or more in 24-hour mortality and 88% power to detect a difference of 12% or more in 30-day mortality, assuming each alpha=0.044, two-sided test, and 11% 24-hour mortality and 23% 30-day mortality in the 1:1:1 group. Mantel-Haenszel tests will be used with site as a stratifying variable. We will describe mechanistic drivers and sequelae of TIC and inflammation, and characterize the natural history of the coagulation milieu with resuscitation after severe injury in randomized patients. Given the life-threatening situation and the prospect of benefit in each treatment arm, exception from informed consent will be used. Susanne May, ROC Data Coordinating Center (DCC), is the Principal Investigator (PI) of contact. Gerald van Belle, DCC, is the PI-PROPPR. John Holcomb is PI of the UTHealth Clinical Coordinating Center, a ROC satellite, supervises the Clinical Sites, as well as the laboratory and systems biology components. Barbara Tilley of The UTHealth School of Public Health is the PI of the Data Coordinating Center, a ROC satellite, manages the data, oversees data quality, provides analyses of blinded and unblinded data, provides on-site study monitors, and reports on safety and interim analyses to the Data Safety Monitoring Committee. RELEVANCE: The knowledge gained from this Phase III trial will impact the way in which massively bleeding patients at hospitals are transfused. By making better decisions regarding which patients are most in need of a massive transfusion, and transfusing the right ratio of blood products to mitigate potential traumatic coagulopathies, trauma teams will be afforded an ability to impact populations and lower the amount of otherwise preventable deaths resulting from hemorrhagic shock.