Pediatric Heart Network University of Utah

描述(由申请人提供)： 自2001年以来，犹他州儿科心脏病网络在进行临床研究方面取得的成就，包括方案设计、招募、研究绩效、数据分析和解释以及结果的传播，表明了他们愿意与其他临床中心、数据协调中心和NHLBI合作。 这项研究解决了左心发育不良综合征(HLHS)婴儿生长障碍的重大问题。作为第一项评估不针对心血管系统以促进生长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高的发病率和资源利用率。他们的住院费用在所有类型的出生缺陷中都是最高的，每年超过1.8亿美元。HLHS婴儿在出生后的最初几个月至少要接受两种复杂的姑息性手术：一周前通常行主动脉弓分流术(Norwood手术)；四至六个月时通常行上腔静脉-肺连接术(SCPC)。新生儿心脏手术给这些婴儿带来了显著的代谢压力，许多婴儿在手术时已经营养不良。诺伍德手术后，婴儿的体重随着年龄的增长急剧下降，并且在非伍德出院和SCPC手术之间继续发育不良。生长不良是导致长时间住院、死亡或移植以及神经发育受损的最重要的风险因素之一。旨在改善血流动力学和特定喂养方案的药物未能改善这些婴儿的生长。 氧雄酮是一种合成代谢类固醇，已在临床上常规使用了30多年。这种药物几乎没有副作用，而且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发育，包括患有特纳综合征的女孩。我们建议进行一项多中心、随机、双盲、安慰剂对照试验，以评估短程(30天)的氧雄酮治疗对促进HLHS婴儿生长的影响。其具体目的是：1)评估氧雄酮治疗对生长发育、住院病程和神经发育结局的有效性；2)描述氧雄酮治疗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昂的医疗费用。这些婴儿在出生后的头几个月发育不良，增加了他们住院时间较长、神经发育不良、心脏移植或死亡的风险。旨在改善血流动力学的药物或特定的喂养方法并不能改善生长。氧雄酮是一种帮助其他儿童增加体重的药物，如果成功，氧雄酮疗法将代表着一项重大突破，通过改善结局和减少HLHS婴儿的资源利用来影响该领域。

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.