Pediatric Heart Network North Carolina Consortium

儿科心脏网络北卡罗莱纳州联盟

• 批准号: 7489928
• 负责人: JENNIFER S LI
• 金额: $ 27.85万
• 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/7489928
• 关键词: Academic Medical Centers; Adult; Adverse event; Affect; Age-Years; Aldosterone; Aldosterone Receptors; Angiotensin-Converting Enzyme Inhibitors; Biological Markers; Blood Circulation; Brain natriuretic peptide; Cardiac Surgery procedures; Cardiopulmonary; Cardiovascular system; Child; Child health care; Childhood; Chronic; Cicatrix; Clinic; Clinical; Clinical Research; Clinical Trials; Clinical Trials Network; Collagen; Common Ventricle; Congenital Heart Defects; Cross-Sectional Studies; Defect; Development; Digoxin; Dilated Cardiomyopathy; Diuretics; Doppler Echocardiography; Double-Blind Method; Echocardiography; Endothelial Cells; Enrollment; Ensure; Exercise; Exercise stress test; Fibrosis; Fontan Procedure; Frequencies; Functional disorder; Funding; Genetic Polymorphism; Health system; Heart; Heart Diseases; Heart Hypertrophy; Heart failure; Hypertrophy; Hypoplastic Left Heart Syndrome; Infant; Institution; Magnetic Resonance Imaging; Measures; Mineralocorticoid Receptor; Myocardial; Myocardial Infarction; North Carolina; Operative Surgical Procedures; Outcome Measure; Oxygen Consumption; Parents; Patient Care; Patient Recruitments; Patients; Peptides; Performance; Physiology; Placebos; Population; Population Control; Process; Procollagen; Progress Reports; Pulmonary Circulation; Quality of life; Quality-of-Life Assessment; Questionnaires; Randomized; Renin; Renin-Angiotensin-Aldosterone System; Role; Rural; Safety; Sample Size; Serum; Shunt Device; Side; Spironolactone; Staging; Standards of Weights and Measures; Symptoms; System; Testing; Tissues; United States; Universities; Upper arm; Ventricular; Ventricular Remodeling; abstracting; falls; forest; improved; innovation; interstitial; mortality; placebo controlled study; procollagen Type I N-terminal peptide; procollagen Type III-N-terminal peptide; programs; reconstruction; response; skills; success; treatment duration

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Wake Forest University Health Systems（WFUHS）已成立了北卡罗来纳州财团（NCC），参加了儿科心脏病网络网络试验和研究。自1996年以来，我们的三个机构在48多个项目中进行了合作，资金约为5600万美元。每年在我们的诊所接受了300多名先天性心脏缺陷的患者中，有90％以上的先天性心脏缺陷患者在我们的诊所进行了心脏病。我们的患者人群是独一无二的：我们的患者在种族和种族上多样，贫穷和农村地区。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测得的结果。必须确定这些影响以概括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，多机构的，双盲的，安慰剂对照的研究，以评估螺内酯对接受丰丹手术的儿童运动表现的影响：醛固酮阻塞和运动（ABL）。假设：螺内酯将改善6-21岁的方丹患者的运动表现和生活质量。主要目标：确定螺内酯对峰值消耗量的影响。次要目标：通过1）生活质量测量的螺内酯的功效，通过经过验证的措施评估； 2）通过组织多普勒超声心动图评估的心室填充参数； 3）MRI评估的心肌疤痕量； 4）神经激活，BNP；胶原蛋白合成的生物标志物，procollagen I和III肽； 5）肾素血管紧张素醛固酮系统多态性。试验持续时间为六个月。如果使用没有Alpha = 0.05的双面测试，则需要每个治疗组的样本量220，以实现85％的统计能力，以检测螺内酯和安慰剂之间的峰值消耗量的平均差异，如果组之间的峰值氧峰值消耗的预期平均差异为2 ml/kg/min/kg/min，并且组内的标准偏差为7 ml/kg/kg/kg/kg/kg/kg/kg/kg。拟议的研究具有重要意义和创新性：结果可能支持一种新的疗法。它将是对单个心室生理学儿童的药理学治疗迄今为止最大的随机研究；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的反应中的作用。我们还申请临床研究技能发展核心。 （摘要结束）。