Pediatric Heart Network Prairieland Consortium

儿科心脏网络 Prairieland 联盟

基本信息

批准号：
8692574
负责人：
James Cnota
金额：
$ 46.03万
依托单位：
CINCINNATI CHILDRENS HOSP MED CTR
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-01 至 2016-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8692574
关键词：
18 year old Acetylcysteine Acute Acute Renal Failure with Renal Papillary Necrosis Address Adult Affect Age Animals Antioxidants Area Under Curve Attenuated Basic Science Bedside Testings Biological Markers Cardiac Surgery procedures Cardiomyopathies Cardiopulmonary Bypass Cardiovascular system Child Childhood Clinical Clinical Medicine Clinical Research Clinical Trials Combined Modality Therapy Complication Consent Creatinine Creatinine clearance measurement Development Diagnosis Diagnostic Double-Blind Method Early Intervention Early treatment Echocardiography Enrollment Failure Gelatinase A Genomics Heart Hospitals Hour Incidence Injury Intervention Kidney Knowledge Length of Stay Mechanical ventilation Medical Medical center Mission Morbidity - disease rate Myocardial Operative Surgical Procedures Outcome Output Pathogenesis Patient Recruitments Patients Pediatric Hospitals Pilot Projects Placebo Control Placebos Plasma Principal Investigator Proteomics Public Health Randomized Relative (related person)Renal Replacement Therapy Renal function Research Risk Secondary to Serum Services Severities Sodium Bicarbonate Stratification Supportive care Technology Testing Therapeutic Therapeutic Effect Therapeutic Intervention Time Translating Treatment Failure Troponin Urine base burden of illness clinically significant experience improved mortality novel patient population point of care prevent programs prospective service utilization standard care trial comparing urinary

项目摘要

DESCRIPTION (provided by applicant): This Clinical Center (Prairieland Consortium) is a collaborative effort among the Pediatric Cardiovascular Programs at Cincinnati Children's Hospital Medical Center, Cincinnati, OH and Riley Hospital for Children, Indianapolis, IN. Previous experience in the Pediatric Heart Network (PHN), an outstanding research team and the Consortium's combined patient population, characterized by >500 open heart surgeries and >20,000 echocardiograms annually, support an ability to contribute significantly to patient recruitment for PHN trials. The Clinical Trial we propose addresses an important gap in clinical medicine by translating bench discovery of biomarker technology into a pediatric multicenter clinical trial. Acute kidney injury (AKI) is a common complication of cardiopulmonary bypass (CPB), affecting adult and pediatric patients and significantly increasing the risk of mortality and medical services utilization. AKI treatment has traditionally been limited to supportive care or renal replacement therapy for severe cases. A major reason for treatment failure has been the unavoidable delay in initiating treatment secondary to lack of early biomarkers for AKI, akin to troponins in acute myocardial injury. Our research team identified neutrophil gelatinase-associated lipocalin (NGAL) as a diagnostic biomarker and showed that plasma and urine NGAL levels 2 hours after initiation of CPB reliably predict AKI development. Availability of a point-of-care (POC) NGAL test provides a means to diagnose AKI risk within an appropriate therapeutic "window of opportunity". Our central hypothesis is that early treatment of pediatric patients at risk for AKI based upon NGAL POC testing will reduce the incidence or mitigate the severity of AKI following CPB. We propose a randomized, double-blind trial comparing sodium bicarbonate (NaHCO3), the anti-oxidant N-acetylcysteine (NAC) or combination therapy to placebo in post-CPB pediatric patients, ages 1 month to 18 years, at risk for AKI based on early elevation of plasma NGAL. Assuming the participation of all 8 core PHN Centers with a conservative estimated minimum yearly volume of 200-250 eligible patients and a consent rate of 50%, study enrollment would be completed in 18- 23 months, allowing for analysis and dissemination of results within a 3 year time period. RELEVANCE: AKI is relevant to public health as it is a common, clinically significant problem following CPB in patients of all ages. Use of a biomarker for assessment of AKI risk provides for the first time an opportunity for early intervention to reduce the incidence or mitigate the severity of AKI following CPB and thereby prevent associated morbidity and mortality. Thus, the proposed research is relevant to NIH's mission because it will provide fundamental knowledge necessary to reduce illness burden from AKI.

描述（由申请人提供）：这个临床中心（Prairieland Consortium）是俄亥俄州辛辛那提市辛辛那提儿童医院医疗中心和印第安纳州印第安纳波利斯儿童的辛辛那提儿童医院医疗中心的儿科心血管计划的合作努力。先前在小儿心脏网络（PHN）的经验，一个杰出的研究团队和该财团的组合患者人群，其特征是> 500次开放心脏手术和> 20,000次超声心动图，并支持对PHN试验的患者招聘贡献的能力。我们提出的临床试验通过将生物标志物技术的基准发现转化为儿科多中心临床试验，解决了临床医学的重要差距。急性肾脏损伤（AKI）是心肺旁路（CPB）的常见并发症，影响成人和小儿患者，并显着增加了死亡率和医疗服务利用的风险。传统上，AKI治疗仅限于严重病例的支持性护理或肾脏替代疗法。治疗失败的主要原因是不可避免地延迟了继发于AKI早期生物标志物的治疗，类似于急性心肌损伤中的肌钙蛋白。我们的研究小组将中性粒细胞明胶酶相关的脂肪蛋白（NGAL）确定为诊断生物标志物，并表明CPB开始后2小时血浆和尿液NGAL水平可靠地预测了AKI的发展。可以在适当的治疗“机会之窗”中诊断AKI风险的手段（POC）NGAL测试提供了一种方法。我们的中心假设是，基于NGAL POC测试，对处于AKI风险的小儿治疗将降低CPB后AKI的发生率或减轻AKI的严重程度。我们提出了一项随机的双盲试验，以比较碳酸氢钠（NAHCO3），抗氧化剂N-乙酰半胱氨酸（NAC）或联合疗法与CPB后儿科患者的安慰剂，年龄为1个月至18岁，面临AKI基于AKI的风险，血浆ngal的早期升高。假设所有8个核心PHN中心的参与度具有保守的估计最低年度为200-250名合格患者的年度最低量，并且同意率为50％，则研究入学率将在18-23个月内完成，从而允许分析和传播结果。 3年时间。相关性：AKI与公共卫生相关，因为在所有年龄段的患者中，CPB是常见的，临床上的重要问题。使用生物标志物来评估AKI风险，这是首次提供早期干预的机会，以减少CPB后AKI的发生率或减轻AKI的严重性，从而防止相关的发病率和死亡率。因此，拟议的研究与NIH的使命有关，因为它将提供减轻AKI疾病负担所必需的基本知识。