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

项目概要/摘要 胃食管反流病（GERD）基于症状的诊断及其经验性治疗的流行， 高风险住院婴儿的实践差异仍然很大。先前的临床试验数据缺乏生理学- 基于客观的诊断证据和治疗。 GERD 的诊断标准常常不充分，并且 GERD 治疗的相对风险、益处和适应症尚不清楚。因此，知识差距仍然存在，并且 GERD 诊断可能会额外花费 7 万美元，并且每个婴儿需要住院 30 天。客观、有效、 迫切需要循证疗法。几乎所有婴儿都在新生儿重症监护室 (NICU) 有症状时，二十四小时 pH 阻抗 (pH-Imp) 测试可以客观诊断并检测 GERD 的病理生理机制。因此，本研究的总体目标是进行单中心 随机对照试验 (RCT) 旨在检验常见疗法 [自然疗法] 效果的中心假设 成熟、抑酸质子泵抑制剂 (PPI) 或使用添加大米 (AR) 配方的增稠饲料] 在高危婴儿中，根据 pH-Imp 定义的 GERD 标准校正成熟年龄低于 6 个月。 其基本原理是完善新的诊断标准并严格研究随机疗法的影响 实现创造有效、简化、循证和可扩展治疗的长期目标 算法。 我们将在以下具体目标中检验这一假设： 目标 1：进行 RCT 来评估和比较 干预措施对主要临床终点（经口喂养的改善和缺乏 麻烦的症状）来检验 AR 优于自然成熟和 PPI 的工作假设。目标 2： 评估 pH-Imp 特性并测试 pH-Imp 机制在不同类型之间存在差异的工作假设 a) 指定疗法，以及 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 pH-Imp 指标的新颖组合来诊断和管理 NICU 婴儿的 GERD 具有目标分层（GERD 严重程度和喂养技能）的随机分配，以确定真实的 对临床和机械特征的治疗效果。预期结果将确定诊断 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，因为所获得的知识将提供诊断依据、框架以及科学和 未来研究的经济原理，以进一步完善整个儿科年龄范围的治疗方法。我们期望 制定 GERD 预防和治疗策略的新基准，这将对 GERD 产生积极影响 通过改善消化健康、整体营养和生长来提高婴儿和父母的生活质量，所有这些都与 NIH (NIDDK) 的使命。

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).