SILENT CEREBRAL INFARCT MULTI-CENTER CLINICAL TRIAL

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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.