In 2000, the National Heart, Lung, and Blood Institute (NHLBI) awarded contracts to conduct a randomized, double-blind, placebo-controlled trial in young children with sickle cell disease (SCD) to test the hypothesis that Hydroxyurea (HU) can prevent the onset of chronic end organ damage in children recruited before two years of age. Contracts were awarded to ten Clinical Centers to recruit, enroll, and follow patients to monitor clinical responsiveness to study treatments, to assess growth and development, and to monitor for toxicity from study treatments. Surrogate markers of end organ damage were used to evaluate pulmonary, renal, splenic, and brain function as well as developmental milestones. One Medical Coordinating Center was awarded to oversee drug distribution, coordinate central laboratory functions, perform data collection and analysis, and conduct clinical sites visits to monitor study performance. The trial enrolled 193 subjects with SCD between the ages of 9 and 17 months from October 2003 to June 2007. Subjects remained on study drug for a period of two years. HU demonstrated substantial clinical benefit without serious toxicity in this cohort of very young children. In 2008, a follow-up study was added to the contracts to provide structured follow-up of the children after they completed their two years on study drug. The purpose of the initial Follow-Up Study is to characterize the long-term toxicities and unexpected risks (if any) associated with treatment with HU at an early age. Information obtained from this follow-up study is vitally important to understanding the risks and benefits of early treatment, and ultimately for creation of an optimal paradigm for HU therapy in young children with sickle cell anemia. The follow-up study ends in December 2011.
