Pathophysiological Evidence Driven Management of GERD in Neonatal ICU Infants: Randomized Controlled Trial

新生儿 ICU 婴儿 GERD 的病理生理学证据驱动管理：随机对照试验

• 批准号: 10717324
• 负责人: Sudarshan R Jadcherla
• 金额: $ 66.36万
• 依托单位: RESEARCH INST NATIONWIDE CHILDREN'S HOSP
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-15 至 2028-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10717324
• 关键词: Acids; Adverse effects; Age; Algorithms; Benchmarking; Biological Markers; Caring; Categories; Cereals; Characteristics; Childhood; Chronology; Clinic Visits; Clinical; Clinical Trials; Coughing; Data; Diagnosis; Diagnostic; Diagnostic tests; Distal; Eating; Economic Burden; Economics; Effectiveness; Enteral Feeding; Equilibrium; Equipoise; Esophagus; Evaluation; Event; Evidence based practice; Evidence based treatment; Failure; Feeding Methods; Feeds; Future; Gastroesophageal reflux disease; Goals; Growth; Health; Hospitalization; Hour; Infant; Intake; Intervention; Knowledge; Length of Stay; Measurement; Mission; Modification; National Institute of Diabetes and Digestive and Kidney Diseases; Neonatal; Neonatal Intensive Care Units; Neurologic; Nutrient; Oral; Outcome; Parents; Pathologic; Peripheral; Pharmaceutical Preparations; Physiological; Population; Pregnancy; Prevalence; Probability; Proton Pump Inhibitors; Provider; Public Health; Quality of life; Randomized; Randomized, Controlled Trials; Relative Risks; Research; Research Personnel; Rice; Safety; Severities; Severity of illness; Stratification; Symptoms; Testing; Therapeutic; Therapeutic Effect; Time; Treatment Efficacy; Tube; United States National Institutes of Health; Variant; Vomiting; Work; arm; associated symptom; clinical efficacy; comparative efficacy; cost; decision making algorithm; design; diagnostic algorithm; diagnostic criteria; disease diagnosis; effective therapy; efficacy testing; electric impedance; evidence base; feeding; follow-up; high risk; high risk infant; hospital readmission; improved; indexing; novel; novel diagnostics; nutrition; primary endpoint; primary outcome; programs; response; secondary outcome; skills; socioeconomics; stem; success; treatment group; treatment response; unnecessary treatment

PROJECT SUMMARY/ABSTRACT The prevalence of symptom-based diagnosis of gastroesophageal reflux disease (GERD), its empiric treatment, and practice variation in high-risk hospitalized infants remain high. Prior clinical trials data lack physiological- based, objective diagnostic evidence and treatment. GERD is frequently diagnosed by inadequate criteria, and the relative risks, benefits, and indications of GERD therapies are unclear. Thus, gaps in knowledge persist, and a GERD diagnosis can cost an extra $70k and 30 days of hospitalization per infant. Objective, effective, evidence-based therapies are critically needed. As nearly all infants in the neonatal intensive care unit (NICU) are symptomatic, twenty-four-hour pH-Impedance (pH-Imp) testing can diagnose objectively and detect mechanisms of pathophysiologic GERD. Therefore, this study’s overall objective is to conduct a single-center randomized control trial (RCT) to test the central hypothesis that the effects of common therapies [natural maturation, acid suppression-proton pump inhibitor (PPI), or thickened feeds using added rice (AR) formula] are distinct in high-risk infants, under six months corrected maturational age with pH-Imp defined criteria for GERD. The rationale is to refine novel diagnostic criteria and rigorously investigate the impact of randomized therapies to achieve the long-term goal of creating effective, simplified, evidence-based, and scalable treatment algorithms. We will test this hypothesis in the following Specific Aims: Aim 1: Conduct the RCT to evaluate and compare the efficacy and safety of interventions on the primary clinical endpoint (oral feeding improvement and absence of troublesome symptoms) to test the working hypothesis that AR is superior to natural maturation and PPI. Aim 2: Evaluate pH-Imp characteristics and test the working hypotheses that pH-Imp mechanisms are distinct between a) assigned therapies, and b) clinical success and failure. This project challenges current empiric approaches to diagnosing and managing GERD in NICU infants by using both a novel combination of pH-Imp metrics and randomized allocations with targeted stratification (GERD severity and feeding skills) to determine true therapeutic effects on clinical and mechanistic characteristics. The anticipated outcomes will identify diagnostic algorithms for determining GERD and effective treatment approaches. In addition, the proposed research is significant because the knowledge gained will provide the diagnostic basis, framework, and scientific and economic rationale for future studies to further refine therapies across the pediatric age spectrum. We expect new benchmarks to develop preventative and therapeutic strategies for GERD, which will positively impact the quality of life for infants and parents by improving digestive health, overall nutrition, and growth, all relevant to the mission of NIH (NIDDK).

项目摘要/摘要 基于症状的胃食管反射疗法（GERD）的患病率，其经验疗法， 高危住​​院婴儿的练习差异仍然很高。先前的临床试验数据缺乏生理 - 基于客观的诊断证据和治疗。 GERD经常被标准不足诊断，并且 GERD疗法的相对风险，益处和适应症尚不清楚。那，知识差距持续存在，并且 GERD诊断可能会额外花费7万美元和30天的住院时间。客观，有效， 迫切需要循证疗法。由于新生儿重症监护病房（NICU）几乎所有婴儿 是有症状的，二十四小时的pH阻抗（pH-IMP）测试可以客观地诊断并检测 病理生理GERD的机制。因此，这项研究的总体目标是进行单中心 随机对照试验（RCT），以检验中心假设，即常见疗法的作用[自然疗法 成熟，酸抑制 - 普罗替型泵抑制剂（PPI）或使用添加的大米（AR）配方的增厚饲料是 在高风险婴儿中，六个月以下的材料年龄在pHIMP定义的GERD标准下校正了。 理由是完善新的诊断标准，并严格研究随机疗法的影响 为了实现创建有效，简化，基于证据和可扩展处理的长期目标 算法。 我们将在以下特定目的中检验这一假设：目标1：进行RCT评估和比较 干预措施对主要临床终点的功效和安全性（口服进食和缺乏 麻烦的症状）测试AR优于自然成熟和PPI的工作假设。目标2： 评估pHIMP特征并测试工作假设，即PH-IMP机制在 a）分配疗法，b）临床成功和失败。该项目挑战了当前的经验方法 通过使用新颖的pH-IMP指标和 具有针对性分层的随机分配（GERD严重性和进食技巧）以确定真实 对临床和机械特征的治疗作用。预期的结果将确定诊断 用于确定GERD和有效治疗方法的算法。此外，拟议的研究是 意义重大，因为获得的知识将提供诊断基础，框架和科学的基础，并且 未来研究的经济理由，以进一步完善小儿年龄谱的疗法。我们期望 为GERD制定预防和治疗策略的新基准，这将对 婴儿和父母的生活质量通过改善消化健康，整体营养和增长，都与 NIH（NIDDK）的任务。