OPTIMIZING STROKE PREVENTION IN SC ANEMIA CHILDREN

描述 (根据申请者的摘要改编)中风发生在大约11%的 20岁前患有纯合子镰状细胞性贫血的儿童。最近， 镰状细胞性贫血(STOP)中的中风预防试验显示，高危人群 患者可以通过经颅多普勒(TCD)超声进行识别 定期输血可降低每年首次输血的发病率 中风高危患者从10%增加到1%。大多数处于停顿状态的儿童恢复正常 在输血时恢复到正常的TCD-意味着向低中风风险转变。这个 拟议的研究(Stop II)建立在Stop的基础上，以优化高... 有风险的病人。这种非常有效的预防措施的临床接受度 由于缺乏关于是否以及何时可以输血的信息，战略受到限制 对治疗有反应的患者在治疗30个月后停止。一 在接下来的18个月内，将在36个月内随机抽取100名儿童- 在结束招募后(即每名患者18-54个月的随访)。 有重大动脉疾病证据的儿童磁共振 血管造影术将被排除在外。所有患者将每季度接受一次TCD 考试。将使用复合端点，该端点将包括 恢复到高风险(TCD(&gt；200厘米/秒)或临床中风。患者 恢复到高风险将提供返还输血。TCD，磁性 将阅读和/或阅读共振研究、关键实验室措施和终点 在Stop中，使用集中盲目程序进行裁决被证明是成功的。 假设每年输血终止率保持在1%，如 停止，研究将有90%的能力检测增加到&>10%之后 停止输血。这项研究将优化一级预防 战略被证明是有效的，对患有以下疾病的儿童具有巨大的潜力 镰状细胞性贫血。

DESCRIPTION (Adapted from the applicant's abstract) Stroke occurs in approximately 11% of children with homozygous sickle cell anemia by 20 years of age. Recently, The Stroke Prevention Trial in Sickle Cell Anemia (STOP) showed that high-risk patients can be identified with transcranial Doppler (TCD) ultrasound and that periodic blood transfusions can reduce the annual incidence of first time stroke in high-risk patients from 10% to <1%. Most children in STOP reverted to normal TCD-signifying change to low stroke risk-while on transfusion. The proposed research (STOP II) builds on STOP to optimize the treatment of high- risk patients. Clinical acceptance of this remarkably effective preventive strategy is limited by lack of information on if and when transfusion can be halted after 30 months of treatment in patients who respond to therapy. One hundred children will be randomized over 36 months within 18 months of follow- up after closing recruitment (i.e., 18-54 months of follow-up per patient). Children with evidence of significant arterial disease on Magnetic Resonance Angiography will be excluded. All patients will receive quarterly TCD examinations. A composite endpoint will be used that will consist of reversion to high-risk (TCD (>200 cm/sec) or clinical stroke. Patients who revert to high risk will be offered return to transfusion. TCD, magnetic resonance studies, key laboratory measures and endpoints will be read and/or adjudicated using centralized blinded procedures proved successful in STOP. Assuming the annual endpoint rate on transfusion remains at <1% as seen in STOP, the study will have 90% power to detect an increase to >10% after halting transfusion. This research will optimize the primary prevention strategy proven effective in STOP with significant potential for children with sickle cell anemia.