OPTIMIZING STROKE PREVENTION IN SICKLE CELL ANEMIA

（改编自申请人摘要）中风发生在大约11%的 20岁时患有纯合子镰状细胞性贫血的儿童。 近日 镰状细胞性贫血的中风预防试验（STOP）显示， 患者可以通过经颅多普勒（TCD）超声识别， 定期输血可以减少首次输血的年发病率。 高风险患者的中风率从10%降至<1%。 STOP中的大多数儿童 正常TCD-意味着改变为低中风风险-而输血。 的 拟议的研究（STOP II）建立在STOP的基础上，以优化高血压的治疗， 风险患者。 临床上接受这种非常有效的预防 由于缺乏关于输血是否以及何时可以 在对治疗有反应的患者中，治疗30个月后停止。 一 在随访的18个月内，将在36个月内对100名儿童进行随机分组- 在结束招募之后（即，每例患者随访18-54个月）。 磁共振显示有明显动脉疾病证据的儿童 将排除血管造影。 所有患者将接受季度TCD 考试 将使用一个复合终点，该终点将包括 逆转为高危（TCD>200 cm/sec）或临床卒中。 的患者 恢复到高风险将提供回输。 TCD，磁性 将阅读共振研究、关键实验室指标和终点，和/或 使用集中设盲程序裁定的患者在STOP中证明是成功的。 假设输血的年终点率保持在<1%，如图所示， 停止，研究将有90%的把握度检测到增加至>10%， 停止输血 这项研究将优化一级预防 战略在STOP中证明是有效的，对儿童有很大的潜力， 镰状细胞性贫血

(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.