TCD with Transfusions Changing to Hydroxyurea - SDMC

项目总结/摘要 中风发生在5 - 10%的SCA儿童中，是一种破坏性的临床事件，可导致严重的 运动和神经认知缺陷。为了帮助预防初始（原发性）卒中，年轻SCA患者可以 定期接受TCD筛查，以识别脑血管系统中动脉流速升高的儿童， 这预示着原发性中风风险的增加。时间平均最大速度（TAMV）儿童 大脑中动脉（MCA）或颈内动脉（ICA）升高至"异常"范围 （e200 cm/sec），慢性红细胞输注显著降低原发性卒中的风险。在这种情况下， 输血可以预防首次中风，但具有严重的副作用，限制了其长期应用。输血 传播感染因子，导致红细胞同种抗体或自身抗体形成，并导致铁 超载。输血获得性铁过载被认为是年轻人发病率和死亡率的来源 SCA患者接受输血以预防原发性卒中。螯合疗法可以帮助预防 铁的积累，但难以容忍和不遵守是常见的。输血的替代方法 显然需要一级预防中风的预防措施，特别是还提供机会， 解决输血获得性铁过载的问题。我们提出了一项III期随机临床试验， 患有镰状细胞性贫血（SCA）和经颅多普勒（TCD）速度异常的儿童，称为"TCD 输血改为羟基脲"（TWiTCH）试验。我们的假设是， 维持与红细胞输注相似的TCD速度，因此作为非劣效治疗， SCA高危儿童卒中的一级预防。TWiTCH试验的主要目的是比较 标准治疗（输血）替代治疗（羟基脲）维持TCD速度 长期输血的SCA儿童TCD速度异常。TWiTCH的其他目标包括 标准治疗与替代治疗原发性卒中发生率的比较，频率的确定 非卒中神经系统事件和其他镰状细胞相关事件，铁过载的管理， 生长发育评估、不良事件记录和生活质量测量。

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.