From Berry Consultants, LLC (E.K., K.V., R.J.L.), Austin, Texas; Division Critical Care, Department of Pediatrics (P.C.S.), Washington University in St Louis, St Louis, Missouri; Divisions of Hematology/Oncology and Critical Care Medicine, Department of Pediatrics (M.E.S.), Department of Laboratory Medicine and Pathology (N.D.Z.), University of Minnesota, Minneapolis, Minnesota; Department of Emergency Medicine (R.J.L.), Harbor-UCLA Medical Center; Los Angeles Biomedical Research Institute (R.J.L.), Torrance; and Department of Emergency Medicine (R.J.L.), David Geffen School of Medicine at UCLA, Los Angeles, California.
J Trauma Acute Care Surg. 2018 Jun;84(6S Suppl 1):S41-S46. doi: 10.1097/TA.0000000000001876.
Storage of platelets at 4°C compared with 22°C may increase both hemostatic activity and storage duration; however, the maximum duration of cold storage is unknown. We report the design of an innovative, prospective, randomized, Bayesian adaptive, "duration finding" clinical trial to evaluate the efficacy and maximum duration of storage of platelets at 4°C.
Patients undergoing cardiac surgery and requiring platelet transfusions will be enrolled. Patients will be randomized to receive platelets stored at 22°C up to 5 days or platelets stored at 4°C up to 5 days, 10 days, or 15 days. Longer durations of cold storage will only be used if shorter durations at 4°C appear noninferior to standard storage, based on a four-level clinical hemostatic efficacy score with a NIM of a half level. A Bayesian linear model is used to estimate the hemostatic efficacy of platelet transfusions based on the actual duration of storage at 4°C.
The type I error rate, if platelets stored at 4°C are inferior, is 0.0247 with an 82% probability of early stopping for futility. With a maximum sample size of 1,500, the adaptive trial design has a power of over 90% to detect noninferiority and a high probability of correctly identifying the maximum duration of storage at 4°C that is noninferior to 22°C.
An adaptive, duration-finding trial design will generate Level I evidence and allow the determination of the maximum duration platelet storage at 4°C that is noninferior to standard storage at 22°C, with respect to hemostatic efficacy. The adaptive trial design helps to ensure that longer cold storage durations are only explored once substantial supportive data are available for the shorter duration(s) and that the trial stops early if continuation is likely to be futile.
与 22°C 相比，4°C 储存血小板可能会增加止血活性和储存时间；然而，冷储存的最长时间尚不清楚。我们报告了一项创新性的、前瞻性的、随机的、贝叶斯适应性的“持续时间发现”临床试验的设计，以评估 4°C 储存血小板的疗效和最长时间。
接受心脏手术并需要血小板输注的患者将被纳入研究。患者将被随机分配接受在 22°C 下储存 5 天的血小板或在 4°C 下储存 5 天、10 天或 15 天的血小板。只有在基于四级临床止血疗效评分（NIM 为半级）的情况下，4°C 下较短的储存时间显示出不亚于标准储存的非劣效性，才会使用更长的冷储存时间。贝叶斯线性模型用于根据 4°C 下的实际储存时间估计血小板输注的止血疗效。
如果 4°C 下储存的血小板较差，则 I 型错误率为 0.0247，无效的早期停止概率为 82%。在最大样本量为 1500 的情况下，适应性试验设计有超过 90%的概率检测到非劣效性，并且有很高的概率正确确定与 22°C 相比非劣效的 4°C 下最长储存时间。
适应性、持续时间发现试验设计将产生 I 级证据，并允许确定与标准 22°C 储存相比，4°C 下血小板储存的最长时间不劣于止血功效。适应性试验设计有助于确保只有在有大量支持较短储存时间的数据时才探索更长的冷储存时间，并且如果继续下去可能无效，则试验会提前停止。
