TCD with Transfusions Changing to Hydroxyurea - SDMC

项目摘要/摘要 中风发生在5-10%患有SCA的儿童中，是一种破坏性的临床事件，导致严重的 运动和神经认知缺陷。为了帮助预防最初的(原发性)中风，患有SCA的年轻患者可以 接受周期性的TCD筛查以识别脑血管系统中动脉血流速度升高的儿童， 这预示着原发性中风风险的增加。对于具有时间平均最大速度(TAMV)的儿童 大脑中动脉(MCA)或颈内动脉(ICA)升高到“异常”范围 (e200厘米/秒)，慢性红细胞输注显著降低了原发性中风的风险。在这种情况下， 输血可以预防首次中风，但有严重的副作用，限制了它们的长期效用。输血 传播感染性物质，导致红细胞同种抗体或自身抗体的形成，并导致铁 超载。输血获得性铁超载被认为是年轻人发病率和死亡率的来源 SCA患者接受输血预防原发性卒中。螯合疗法有助于预防 铁蓄积，但难以容忍和不合规的现象屡见不鲜。一种替代输血的方法 显然，一级预防中风的预防措施是必要的，特别是也提供了一个机会 解决输血获得性铁超载的问题。我们建议进行一项第三阶段的随机临床试验 镰状细胞性贫血(SCA)和经颅多普勒(TCD)速度异常的儿童称为TCD 输液改为羟基尿素“(Twitch)试验。我们的假设是羟基尿素可以 保持与红细胞输注相似的经颅多普勒血流速度，因此作为一种非劣势疗法，对于 SCA高危儿童的一级卒中预防。抽搐试验的主要目的是比较 维持TCD血流速度的标准疗法(输液)到替代疗法(羟基尿素) 慢性输液治疗SCA患儿TCD血流速度异常。Twitch的其他目标包括 原发卒中发生率的标准与替代疗法的比较，频率的确定 非中风神经事件和其他镰状细胞相关事件，铁超载的管理， 评估生长发育，记录不良事件，测量生活质量。

Project Summary/Abstract Stroke occurs in 5-10% of children with SCA, and is a devastating clinical event that results in severe motor and neurocognitive deficits. To help prevent an initial (primary) stroke, young patients with SCA can receive periodic TCD screening to identify children with elevated arterial velocities in the cerebral vasculature, which portends increased primary stroke risk. For children with time-averaged maximum velocities (TAMV) in the middle cerebral artery (MCA) or internal carotid artery (ICA) elevated to the "abnormal" range (e200cm/sec), chronic erythrocyte transfusions significantly lower the risk of primary stroke. In this setting, transfusions can prevent first stroke but have serious side-effects limiting their long-term utility. Transfusions transmit infectious agents, lead to erythrocyte alloantibody or autoantibody formation, and result in iron overload. Transfusion acquired iron overload is recognized as a source of morbidity and mortality for young patients with SCA receiving transfusions for prevention of primary stroke. Chelation therapy can help prevent iron accumulation, but is difficult to tolerate and non-compliance is common. An alternative to transfusion prophylaxis for primary stroke prevention is clearly needed, especially one that also provides an opportunity to address the issue of transfusion acquired iron overload. We propose a Phase III randomized clinical trial for children with sickle cell anemia (SCA) and abnormal Transcranial Doppler (TCD) velocities, termed the "TCD With Transfusions Changing to Hydroxyurea" (TWiTCH) trial. Our hypothesis is that hydroxyurea can maintain a similar TCD velocity as erythrocyte transfusions, and therefore serve as non-inferior therapy, for primary stroke prevention in high risk children with SCA. The primary aim of the TWiTCH trial is to compare standard therapy (transfusions) to alternative therapy (hydroxyurea) for maintenance of TCD velocities in children with SCA on chronic transfusions for abnormal TCD velocities. Additional aims of TWiTCH include comparison of standard to alternative therapy for incidence of primary stroke, determination of the frequency of non-stroke neurological events and other sickle cell-related events, management of iron overload, assessment of growth and development, recording of adverse events, and measurement of quality of life.