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.
