Pediatric Heart Network North Carolina Consortium

儿科心脏网络北卡罗莱纳州联盟

• 批准号: 7127027
• 负责人: Page A Anderson
• 金额: $ 29.84万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7127027
• 关键词: adolescence (12-20); aldosterone; aldosterone inhibitor; biomarker; clinical research; clinical trials; collagen; congenital heart disorder; cooperative study; drug screening /evaluation; exercise; heart disorder chemotherapy; heart function; heart surgery; hormone regulation /control mechanism; human subject; human therapy evaluation; medically underserved population; middle childhood (6-11); neurohormones; oxygen consumption; patient oriented research; pediatric pharmacology; pediatrics; postoperative state; quality of life; renin angiotensin system; scars; spironolactone

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).

描述（由申请人提供）： 杜克大学医学中心、东卡罗莱纳大学（ECU）和维克森林大学卫生系统（WFUHS）组成了北卡罗来纳州联盟（NCC），参与儿科心脏病网络试验和研究。自1996年以来，我们的三个机构在48个以上的项目中进行了合作，资金约为5 600万美元。在我们中心接受心脏直视手术的300多名先天性心脏病患者中，每年有90%以上的患者在我们的诊所接受随访。我们的患者群体是独特的：我们的患者是种族和种族多样化，贫困和农村。我们的患者遇到的挑战和独特优势可能会影响临床试验中测量的结果。必须确定这些影响，以推广PHN临床试验的结果，以涵盖美国各地的患者人群。我们提出了一项随机、多机构、双盲、安慰剂对照研究，以评估螺内酯对接受Fontan手术的儿童运动能力的影响：醛固酮阻滞和运动（ABLE）。假设：螺内酯将改善6-21岁Fontan患者的运动表现和生活质量。主要目的：确定螺内酯对峰值耗氧量的影响。次要目的：确定螺内酯的疗效，通过1）生活质量，通过验证的措施评估; 2）心室充盈参数，通过组织多普勒超声心动图评估; 3）心肌瘢痕的数量，通过MRI评估; 4）神经激素活化，BNP;胶原合成的生物标志物，前胶原I和III肽;和5）肾素血管紧张素醛固酮系统多态性。试验期限为六个月。每个治疗组需要220例样本量，以达到85%的统计把握度，使用双侧检验（α = 0.05）检测螺内酯和安慰剂之间峰值耗氧量的平均差异，如果组间峰值耗氧量的预期平均差为2 ml/kg/min，组内标准差为7 ml/kg/min，这项研究具有重要意义和创新性：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;将评估醛固酮拮抗作用影响这些儿童的潜在机制;将评估RAAS多态性在这些儿童对药物治疗反应中的作用。我们还申请了临床研究技能发展核心。(End抽象）。