Effectiveness of Physiologic Testing in PPI Non-Responders

PPI 无反应者生理测试的有效性

• 批准号: 9308473
• 负责人: JOHN E PANDOLFINO
• 金额: $ 36.81万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9308473
• 关键词: Acids; Adult; Affect; Algorithms; Biological Markers; Blinded; Catheters; Client satisfaction; Clinic; Clinical; Clinical Management; Clinical Pathways; Competence; Confusion; Data; Development; Diagnosis; Diagnostic; Diagnostic tests; Effectiveness; Endoscopy; Esophageal; Esophagitis; Evaluation; Failure; Functional disorder; Gastroesophageal reflux disease; Goals; Healthcare; Heterogeneity; Hour; Literature; Manometry; Measurement; Measures; Medical; Metaplasia; Methodology; Monitor; Outcome; Pathologic; Patient-Focused Outcomes; Patients; Pharmaceutical Preparations; Physicians; Physiological; Population; Prevalence; Primary Health Care; Protocols documentation; Proton Pump Inhibitors; Quality of life; Questionnaires; Reflux; Refractory; Resistance; Resolution; Resources; Role; Severities; Symptoms; Techniques; Technology; Testing; Translating; Treatment Failure; Treatment Protocols; United States; Wireless Technology; Withdrawal; base; clinical predictors; clinically relevant; cost; cost effective; electric impedance; experimental study; improved; insight; new technology; patient population; personalized care; personalized medicine; predicting response; prospective; response; stem; tool; treatment response; treatment strategy; working group

Project Summary The prevalence of gastroesophageal reflux disease is estimated to be as high as 20% in the United States, and up to 50% of these patients remain symptomatic on proton pump inhibitor (PPI) therapy. Unfortunately, the clinical approach to understand the mechanism of nonresponse is not standardized, and patients will often undergo various esophageal function tests: 1) pH-impedance, 2) wireless pH monitoring over 96 hours, 3) high-resolution impedance manometry (HRIM), and 4) mucosal impedance. Currently significant controversy exists regarding the best technique, optimal study protocol and treatment approach for the PPI non-responder (PPINR) group, resulting in inappropriate resource utilization and a failure to provide effective personalized care. As such, PPINRs contribute to a large healthcare burden in the United States. The first aim of our study is to identify the relevant physiologic parameters of the aforementioned diagnostic tools in their ability to predict PPI requirement. Subsequently, in aim two these results will be applied to guide the formal development of a clinical algorithm for the management of PPINRs with personalized clinical pathways based on mechanism of treatment failure. We will first perform a prospective comparison trial of 240 PPINR subjects at two centers over a 4 year period. Subjects will complete symptom questionnaires and undergo diagnostic testing (pH-impedance on PPI therapy, HRIM, 96-hour wireless pH monitoring off of PPI therapy and mucosal impedance). Those who have a positive pH study and/or resume PPI therapy will receive escalation of acid suppression therapy with dexlansoprazole. Experiments 1a & 1b will compare the ability of 96-hour wireless pH monitoring vs pH impedance to predict PPI requirement and response to dexlansoprazole, respectively. Experiment 1c will explore whether mucosal impedance is equivalent to 96-hour wireless pH monitoring in predicting PPI requirement. Lastly, Experiment 1d will determine whether HRIM metrics can be utilized to determine reflux burden, mechanism and response to treatment. Next, we will develop quality measures for reflux testing in order to develop a simplified management strategy for the PPINR group. The RAND/UCLA Appropriateness Methodology will be utilized with an expert working group to develop formal validated quality measures for reflux testing based on results from aim 1 in addition to the available literature & evidence. This will be conducted over twelve-months (years 4 to 5).

项目摘要 胃食管反流疾病的患病率在美国估计高达20％， 这些患者中，多达50％的患者对质子泵抑制剂（PPI）疗法仍然有症状。不幸的是， 了解无响应机制的临床方法不是标准化的，患者经常会 接受各种食道功能测试：1）pH-阻抗，2）无线pH监测96小时，3） 高分辨率阻抗测压法（HRIM）和4）粘膜阻抗。当前重大争议 关于PPI无反应器的最佳技术，最佳研究方案和治疗方法的存在 （ppinr）组，导致资源利用不当，无法提供有效的个性化 关心。因此，PPinrs在美国造成了巨大的医疗保健负担。 我们研究的第一个目的是确定上述诊断的相关生理参数 具有预测PPI要求的能力的工具。随后，在目标两个中，这些结果将用于指导 具有个性化临床的PPINR的临床算法的正式开发 基于治疗失败机理的途径。 我们将首先在4年的两个中心对240名PPINR受试者进行前瞻性比较试验。 受试者将填写症状问卷并接受诊断测试（PPI的pH-阻抗 治疗，HRIM，96小时的无线pH值监测PPI疗法和粘膜阻抗）。 那些有一个 阳性pH研究和/或恢复PPI治疗将接受酸抑制疗法的升级 右兰索拉唑。实验1A和1B将比较96小时无线pH监测的能力与pH 分别预测PPI要求和对右兰索拉唑的反应的阻抗。 实验1C 探索粘膜阻抗是否相当于预测PPI的96小时无线pH监测 要求。最后，实验1D将确定是否可以利用HRIM指标来确定回流 负担，机制和对治疗的反应。接下来，我们将制定回流测试的质量措施 为了为PPINR组制定简化的管理策略。 Rand/UCLA适当性 方法学将与专家工作组一起使用，以制定正式验证的质量度量 除了可用的文献和证据外，基于AIM 1的结果反流测试。 这将是 进行了十二个月以上（4至5年）。