BABY HUG FOLLOW-UP STUDY II

2000年，国家心脏、肺和血液研究所（NHLBI）授予合同，在患有镰状细胞病（SCD）的幼儿中进行一项随机、双盲、安慰剂对照试验，以验证羟基脲（HU）可以预防两岁前儿童慢性终末器官损伤的假设。合同授予了10个临床中心，以招募、登记和跟踪患者，以监测对研究治疗的临床反应，评估生长和发育，并监测研究治疗的毒性。最终器官损伤的替代标记物被用来评估肺、肾、脾和脑功能以及发育里程碑。一个医疗协调中心被授予监督药品分发、协调中心实验室职能、进行数据收集和分析，并进行临床地点访问以监测研究成果。该试验从2003年10月至2007年6月招募了193名年龄在9至17个月之间的SCD患者。受试者继续服用研究药物两年。在这个非常年幼的儿童队列中，HU显示出实质性的临床益处，没有严重的毒性。2008年，合同中增加了一项后续研究，在这些儿童完成两年的研究药物后，对他们进行有组织的随访。最初的随访研究的目的是描述早期HU治疗相关的长期毒性和意外风险（如果有的话）。从这项随访研究中获得的信息对于了解早期治疗的风险和益处至关重要，并最终为镰状细胞性贫血幼儿的HU治疗创造最佳范例。后续研究将于2011年12月结束。

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. The purpose of the Baby Hug Follow-Up Study II is to provide continued structured follow-up of the children enrolled in the Baby Hug Follow-Up Study I, to characterize the long-term toxicities and unexpected risks (if any) associated with HU treatment at an early age, and to determine if there are clinical benefits from the treatments. Collection and ongoing evaluation of growth and development and clinical data are crucial for determination of the long-term effects of HU. The objective is to intensively monitor and assess this unique group of children for growth, development, and clinical status at least through the first decade of life to document any alterations in the natural history of sickle cell disease associated with early HU therapy. The follow-up will include enhanced neuropsychological, brain, cardiac, and pulmonary evaluations. All children enrolled will be followed to a common termination date of December 31, 2016. Results from the Follow-up Study II will improve understanding of the natural history of SCD in young children and in a cohort receiving HU. Whether or not HU reduces organ damage in these children will be established. If HU has a beneficial effect, the standard of care for children with SCD will be permanently altered.