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

项目摘要/摘要 胃食道反流病(GERD)的症状诊断、经验性治疗、 高危住院婴儿的实践差异性仍然很高。之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经常被诊断为不适当的标准， GERD治疗的相对风险、益处和适应症尚不清楚。因此，知识的差距依然存在，而且 GERD的诊断可能会额外花费每个婴儿7万美元和30天的住院时间。客观、有效、 迫切需要循证治疗。几乎所有新生儿重症监护病房(NICU)的婴儿 是否有症状，24小时pH阻抗(pH-Imp)测试可以客观诊断和检测 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)，以检验常见疗法[自然]疗效的中心假设 成熟、酸抑制-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，6个月以下的校正成熟年龄与pH-Imp定义的GERD标准明显不同。 其基本原理是改进新的诊断标准，并严格调查随机治疗的影响 实现创建有效、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：进行随机对照试验，以评估和比较 对主要临床终点的干预的有效性和安全性(改善口腔喂养和缺乏 麻烦的症状)，以检验AR优于自然成熟和PPI的工作假设。目标2： 评估pH-Imp特性并检验pH-Imp机制不同于 A)指定的治疗方法，以及b)临床成功和失败。该项目挑战了当前经验主义的方法 一种新的pH-IMP联合检测方法在NICU婴儿GERD诊断和治疗中的应用 通过有针对性的分层(GERD严重程度和喂养技能)随机分配以确定真 治疗对临床和力学特征的影响。预期结果将确定诊断 确定GERD的算法和有效的治疗方法。此外，拟议的研究是 重要的是因为所获得的知识将提供诊断基础、框架和科学 未来研究进一步完善整个儿科年龄段的治疗方法的经济理由。我们预计 制定GERD预防和治疗战略的新基准，这将对 通过改善消化健康、总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 国家卫生研究院(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).