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

项目总结/摘要 胃食管反流病（GERD）的胃镜诊断、经验性治疗、 高危住院婴儿的实践差异仍然很高。之前的临床试验数据缺乏生理学- 客观的诊断证据和治疗。胃食管反流病的诊断标准往往不充分， GERD治疗的相对风险、益处和适应症尚不清楚。因此，知识差距依然存在， GERD诊断可能会花费额外的7万美元和每个婴儿30天的住院治疗。客观，有效， 迫切需要循证疗法。几乎所有新生儿重症监护室（NICU）的婴儿 有症状，24小时pH阻抗（pH-Imp）测试可以客观诊断和检测 病理生理学GERD的机制。因此，本研究的总体目标是进行单中心 随机对照试验（RCT），以检验中心假设，即普通疗法的效果[自然 成熟、酸抑制-质子泵抑制剂（PPI）或使用添加的大米（AR）配方的增稠饲料]是 在6个月以下校正成熟年龄的高风险婴儿中，pH-Imp定义的GERD标准明显。 其基本原理是完善新的诊断标准，并严格调查随机治疗的影响 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：进行随机对照试验， 干预措施对主要临床终点（经口喂养改善和缺乏 麻烦的症状），以测试AR上级自然成熟和PPI的工作假设。目标二： 评价pH-影响特征并测试以下工作假设： a）分配的治疗，和B）临床成功和失败。该项目挑战了目前的经验方法， 通过使用pH-Imp指标的新组合和 随机分配和目标分层（GERD严重程度和喂养技能），以确定真正的 临床和机制特征的治疗效果。预期结果将确定诊断 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， 未来研究的经济学原理，以进一步完善儿科年龄范围内的治疗。我们预计 制定GERD预防和治疗策略的新基准，这将对 通过改善消化系统健康、全面营养和生长，提高婴儿和父母的生活质量， NIH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).