Pediatric Heart Network North Carolina Consortium

描述(由申请人提供)： 杜克大学医学中心、东卡罗来纳大学(ECU)和维克森林大学医疗系统(WFUHS)成立了北卡罗来纳州联盟(NCC)，参与儿童心脏病网络的试验和研究。自1996年以来，我们的三个机构在48个项目上进行了合作，资助金额约为5600万美元。在我们中心接受心内直视手术的300多名先天性心脏病患者中，超过90%的人每年都会在我们的诊所接受随访。我们的患者群体是独一无二的：我们的患者是种族和种族多样化的、贫穷的和农村的。我们的患者遇到的挑战和独特的优势可能会影响临床试验中衡量的结果。必须确定这些影响，以推广PHN临床试验的结果，以涵盖全美的患者群体。我们提出了一项随机、多机构、双盲、安慰剂对照的研究，以评估螺内酯对接受Fontan手术的儿童运动能力的影响：醛固酮阻断和运动(ABLE)。假设：螺内酯可以改善6-21岁Fontan患者的运动能力和生活质量。主要目的：测定螺内酯对最大耗氧量的影响。次要目标：确定螺内酯的疗效：1)生活质量，通过有效的测量方法评估；2)组织多普勒超声心动图评估的心室充盈参数；3)MRI评估的心肌瘢痕形成的数量；4)神经激素激活，BNP；胶原合成的生物标记物，I和III型多肽；5)肾素血管紧张素-醛固酮系统的多态性。试用期为六个月。如果两组间峰值氧耗的预期平均差异为2毫升/公斤/分钟，而组内标准偏差为7毫升/公斤/分钟，则每个治疗组220个样本量将需要达到85%的统计能力，以使用不含α=0.05的双侧检验来检测螺内酯和安慰剂之间的平均峰值氧耗差异。这项拟议的研究具有重大意义和创新性：研究结果可能支持一种新的治疗方法；这将是迄今为止对单心室生理学儿童进行药物治疗的最大规模的随机研究；将评估醛固酮拮抗剂影响这些儿童的潜在机制；将评估RAAS基因多态性在这些儿童对药物治疗的反应中的作用。我们还在申请临床研究技能发展核心。(摘要结束)。

DESCRIPTION (provided by applicant): Duke University Medical Center, East Carolina University (ECU), and Wake Forest University Health Systems (WFUHS) have formed the North Carolina Consortium (NCC) to participate in Pediatric Heart Disease Network trials and studies. Our three Institutions have collaborated since 1996 in over 48 projects with funding of approximately 56 million dollars. Over 90% of the over 300 patients with congenital heart defects who undergo open heart surgery at our Centers are followed in our clinics annually. Our patient population is unique: our patients are ethnically and racially diverse, poor, and rural. The challenges and unique strengths encountered by our patients are likely to affect outcomes measured in clinical trials. These effects must be identified to generalize the results of PHN clinical trials to encompass the patient population across the United States. We propose a randomized, multi-Institutional, double-blind, placebo-controlled study to evaluate the effect of spironolactone on exercise performance in children who have undergone Fontan surgery: aldosterone blockade and exercise (ABLE). Hypothesis: Spironolactone will improve the exercise performance and quality of life of Fontan patients, 6-21 years of age. Primary objective: Determine the effect of spironolactone on peak oxygen consumption. Secondary Objectives: determine efficacy of spironolactone as measured by 1) quality of life, assessed by validated measures; 2) ventricular filling parameters, assessed by tissue Doppler echocardiography; 3) amount of myocardial scarring assessed by MRI; 4) neurohormonal activation, BNP; biomarkers of collagen synthesis, procollagen I and III peptides; and 5) renin angiotensin aldosterone system polymorphisms. The trial duration is six months. A sample size of 220 per treatment group will be required to achieve 85% statistical power to detect mean differences in peak oxygen consumption between spironolactone and placebo, using a two-sided test without alpha = 0.05, if the expected mean difference in peak oxygen consumption between groups is 2 ml/kg/min and the standard deviation within the group is 7 ml/kg/min. The proposed study is significant and innovative: the results may support a new therapy; it will be the largest randomized study to date of pharmacologic treatment of children with single ventricle physiology; potential mechanisms through which aldosterone antagonism affects these children will be assessed; the role of RAAS polymorphisms in these children's response to pharmacologic therapy will be evaluated. We are also applying for a Clinical Research Skills Development Core. (End of Abstract).