Stroke with Transfusions Changing to Hydroxyurea (SWITCH) Trial Data Coordinating

描述（由申请人提供）： 10%的镰状细胞性贫血（SCA）儿童会发生中风，如果不进行治疗，复发的风险非常高。受影响的儿童接受慢性红细胞输注，以防止继发性中风，这是有效的，但由于传染性病原体的传播，红细胞同种抗体和自身抗体的形成，以及铁过载，长期效用有限。输血后获得性铁超载可导致慢性器官损害伴肝纤维化和肝硬化、生长发育不良、心律失常和早期猝死等并发症。去铁胺螯合疗法难以耐受。我们的初步数据表明，羟基脲（HU）是一种有效的替代输血的二级预防中风，也解决了输血获得性铁过载的问题，并可以预防急性血管闭塞事件的SCA，输血停止后，连续放血减少铁负荷。我们提出了一项针对SCA儿童的III期随机临床试验，名为“卒中与改用羟基脲输血”（Stroke with Transfusions Changing to Hydroxyurea，简称OHF），以证明与输血加螯合治疗相比，羟基脲和静脉切开术可以维持可接受的卒中复发率，并显著降低肝脏铁负荷。这是两个配套提案之一：一个是由杜克大学的罗素·威尔同时提交的为SWITCH医疗协调中心提供资金的提案，以及为SWiTCH数据协调中心（DCC）提供资金的提议。DCC将提供非常高质量的协调中心服务，包括研究设计和规划、共同撰写研究文件（方案、操作手册、统计分析计划等），中央交互式患者登记和随机化系统、远程数据输入设施、集中式数据管理、全方位的统计设计和分析服务、设计和生成进展和DSMB报告、DSMB行政支持、参与SWiTCH委员会以及协作准备SWiTCH出版物和演示文稿。

DESCRIPTION (provided by applicant): Stroke occurs in 10% of children with sickle cell anemia (SCA) and has a very high risk of recurrence without therapy. Affected children receive chronic erythrocyte transfusions to prevent a secondary stroke, which are effective but have limited long-term utility due to transmission of infectious agents, erythrocyte alloantibody and autoantibody formation, and iron overload. Transfusion acquired iron overload has morbidity and mortality, including chronic organ damage with hepatic fibrosis and cirrhosis, poor growth and development, cardiac arrhythmias, and early sudden death. Deferoxamine chelation therapy is difficult to tolerate. Our pilot data indicate that hydroxyurea (HU) is an effective alternative to transfusions for secondary stroke prevention that also addresses the issue of transfusion acquired iron overload, and can prevent acute vaso-occlusive events in SCA, after transfusions are discontinued, serial phlebotomy reduces iron burden. We propose a Phase III randomized clinical trial for children with SCA, named Stroke with Transfusions Changing to Hydroxyurea (SWITCH) to demonstrate that hydroxyurea and phlebotomy can maintain an acceptable stroke recurrence and significantly reduce the hepatic iron burden, both in comparison to transfusion plus chelation. This is one of two companion proposals: a proposal to fund the SWiTCH Medical Coordinating Center concurrently submitted by Russell Ware, Duke Univ., and this proposal to fund the SWiTCH Data Coordinating Center (DCC). The DCC will provide very high quality coordinating center services, including study design and planning, co-authoring study documents (Protocol, manuals of operation, statistical analysis plan, etc.), central interactive patient registration and randomization system, remote data entry facilities, centralized data management, the complete range of statistical design and analysis services, design and generation of progress and DSMB reports, DSMB administrative support, participation in SWiTCH committees, and collaboration in the preparation of SWiTCH publications and presentations.