Pediatric Heart Network University of Utah

描述（由申请人提供）： 自2001年以来，犹他州儿科心脏网络在开展临床研究方面取得的成就，包括方案设计、招募、研究执行、数据分析和解释以及结果传播，表明他们愿意与其他临床中心、数据协调中心和NHLBI合作。 本研究探讨了左心发育不良综合征（HLHS）婴儿生长障碍的重要问题。作为第一项评估不针对心血管系统的药物干预有效性的研究，它也展示了创新。HLHS婴儿存活率的提高伴随着相当大的发病率和资源利用。他们的住院费用是任何类型的出生缺陷中最高的，每年超过1.8亿美元。患有HLHS的婴儿在最初几个月内至少接受两种复杂的姑息手术：通常在一周大之前进行主动脉弓重建和肺动脉分流术（诺伍德手术），以及通常在四到六个月大时进行上级腔静脉连接术（SCPC）。新生儿心脏手术对这些婴儿造成了显著的代谢压力，许多婴儿在手术时已经营养不良。在诺伍德手术后，婴儿的体重相对于年龄急剧下降，并且在非伍德出院和SCPC手术之间继续生长不良。生长不良是延长住院时间、死亡或移植以及神经发育受损的最重要风险因素之一。旨在改善血液动力学和特定喂养方案的药物未能改善这些婴儿的生长。 氧甲氢龙是一种合成代谢类固醇，已在常规临床使用超过30年.这种药物副作用小，改善了大面积烧伤儿童的体重增加，改善了身材矮小儿童的生长，包括特纳综合征的女孩。我们提出了一个多中心，随机，双盲，安慰剂对照试验，以评估短期（30天）的氧雄龙治疗，以促进HLHS婴儿生长的影响。具体目标是：1）评价氧雄龙治疗对生长，住院过程和神经发育结果的有效性，2）描述氧雄龙治疗HLHS婴儿的安全性。 相关性：存活的HLHS婴儿有持续的医疗问题和高医疗保健费用。这些婴儿在出生后的头几个月生长不良，增加了他们住院时间更长，神经发育不良，心脏移植或死亡的风险。旨在改善血液动力学的药物或特定的喂养方法不能改善生长。氧甲氢龙是一种药物，已帮助其他儿童体重增加如果成功，氧甲氢龙治疗将是一个重大突破，影响该领域的改善结果和减少资源利用率为婴儿与HLHS。

DESCRIPTION (provided by applicant): Since 2001, the Utah Pediatric Heart Network's accomplishments in performing clinical research, including protocol design, recruitment, study performance, data analysis and interpretation, and dissemination of results, demonstrate their willingness to collaborate with the other clinical centers, the Data Coordinating Center, and NHLBI. This study addresses the significant problem of growth failure in infants with hypoplastic left heart syndrome (HLHS). As the first study to evaluate the effectiveness of a pharmacologic intervention that does not target the cardiovascular system to improve growth, it also demonstrates innovation. The improved survival of infants with HLHS is accompanied by considerable morbidity and resource utilization. Their hospital costs are among the highest of any type of birth defect, exceeding $180,000,000/year. Infants with HLHS undergo at least two complex palliative procedures during their first few months: aortic arch reconstruction with pulmonary artery shunt (Norwood procedure) often before one week of age, and superior cavopulmonary connection (SCPC) usually at four to six months of age. Neonatal cardiac surgery places a significant metabolic stress on these infants, many who are already malnourished at the time of their operation. After the Norwood procedure, infants have a drastic decline in weight for age and continue to grow poorly between Nonwood discharge and the SCPC surgery. Poor growth is one of the most important risk factors for prolonged hospitalization, death or transplant, and impaired neurodevelopment. Medications aimed at improving hemodynamics and specific feeding protocols have failed to improve growth in these infants. Oxandrolone is an anabolic steroid that has been in routine clinical use for over 30 years. The drug has few side effects and has improved weight gain in children with extensive burns and improved growth in children with short stature, including girls with Turner's syndrome. We propose a multicenter, randomized, double- blind, placebo-controlled trial to assess the impact of a short course (30 days) of oxandrolone therapy to promote growth in infants with HLHS. The specific aims are to: 1) evaluate the effectiveness of oxandrolone therapy on growth, hospital course, and neurodevelopmental outcome and 2) describe the safety profile of oxandrolone therapy in infants with HLHS. RELEVANCE: Surviving infants with HLHS have ongoing medical problems and high health care costs. These infants grow poorly in the first months of life, increasing their risk for longer hospitalizations, poor neurodevelopment, and heart transplant or death. Growth is not improved by medications aimed at improving hemodynamics or by specific feeding methods. Oxandrolone is a drug that has helped other children gain weight If successful, oxandrolone therapy would represent a major breakthrough impacting the field by improving outcomes and decreasing the resource utilization for infants with HLHS.