SILENT CEREBRAL INFARCT MULTI-CENTER CLINICAL TRIAL

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 无症状性脑梗塞(SCI)是镰状细胞病(SCD)儿童严重神经系统疾病的最常见原因。这是一项多中心的随机试验，旨在测试患有SCI和SCD的儿童预防性输血治疗是否降低了MRI所定义的随后显性中风或新的SCI的发生率。在约3020名符合筛查条件的6-13岁SCD儿童中，将有1,880人被要求接受核磁共振检查。我们估计20%(376人)将患有脊髓损伤，其中10%(38人)将因TCD测量升高(200厘米/秒)而不符合条件。我们预计，其余338名患者中的60%(203名)将随机接受观察或输血治疗，以保持S的血红蛋白浓度低于30%。在考虑了10%的辍学率和20%的交叉率之后，这个样本量确保了90%的功率来检测新的SCI减少86%。干预持续36个月，每个受试者在12个月时接受MRI和TCD检查，在研究结束时(登记后36个月)接受MRI和认知评估。主要结果是发生中风或新的脊髓损伤。次要目标包括确定：1)预防性输血治疗是否限制智力的进一步下降；以及2)在正式的风险-收益分析中，输血治疗对脊髓损伤的总体好处大于与这种治疗相关的风险。我们预计，这项研究的结果可能会导致同时受SCD和SCI影响的儿童的标准护理做法发生变化。

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. Silent Cerebral Infarct (SCI) is the most common cause of severe neurological disease in children with sickle cell disease (SCD). This is a multi-center, randomized trial to test whether prophylactic blood transfusion therapy in children with SCI and SCD reduces the rate of subsequent overt strokes or new SCI, as defined by MRI. Of approximately 3,020 6-13 year old children with SCD eligible for screening, 1,880 will be asked to undergo MRIs. We estimate that 20% (376) will have SCI and that 10% (38) of these will be ineligible because of an elevated TCD measurement (200 cm/sec). We anticipate that 60% (203) of the remaining 338 will be randomized to either observation or blood transfusion therapy to keep the hemoglobin-S concentration less than 30%. This sample size ensures 90% power to detect an 86% reduction in new SCI, after accounting for 10% drop-out and 20% crossover rates. Intervention lasts for 36 months and each subject will receive a MRI and TCD at 12 months and MRI and cognitive assessment at study exit (36 months after enrollment). The primary outcome is development of stroke or new SCI. Secondary aims include determining whether: 1) prophylactic blood transfusion therapy limits further decline in intellectual abilities; and 2) the overall benefits of blood transfusion therapy for SCI outweigh risks associated with this therapy in a formal risk-benefit analysis. We anticipate results of this study could lead to a change in standard care practices for children affected with both SCD and SCI.