The goal of this clinical trial is to learn if a short course of a potassium-competitive acid blocker (PCAB) test can guide treatment of adults with typical reflux symptoms as effectively as standard physiologic testing with endoscopy and 24-hour pH-impedance monitoring. It will also learn about the safety of PCAB-guided management. The main questions it aims to answer are: * Is PCAB test-guided treatment as effective as physiologic test-guided treatment in improving reflux symptoms after 4 weeks? * How accurate is the PCAB test at detecting pathologic acid reflux compared with 24-hour pH-impedance monitoring? * What medical problems do participants have when receiving PCAB-, proton-pump inhibitor-, or neuromodulator-based treatment? * In this study, researchers will compare two strategies: one group will receive a 7-day course of vonoprazan (PCAB) as a diagnostic test and then treatment guided by the PCAB response, while the other group will undergo endoscopy and 24-hour pH-impedance monitoring with treatment guided by those results. Participants will: * Be randomly assigned to either the PCAB test-guided group or the physiologic test-guided group * Take study medicines by mouth (such as vonoprazan, omeprazole, and/or nortriptyline or matching placebos) for about 4 weeks, depending on their test results and symptom type * Attend scheduled clinic visits for checkups, questionnaires, and safety monitoring * Keep a diary of their reflux symptoms, quality of life, and any use of rescue antacid medicine
This protocol describes a single-center, randomized, controlled, open-label, parallel-group, non-inferiority trial comparing a potassium-competitive acid blocker (PCAB) test-guided strategy with physiologic test-guided management in adults with typical reflux symptoms suggestive of gastroesophageal reflux disease (GERD). The study will enroll approximately 120 participants aged 18-70 years with heartburn, regurgitation, or non-cardiac chest pain, and will exclude patients with Barrett's esophagus, peptic ulcer, prior upper GI surgery, significant comorbidities, or recent use of potent anti-secretory, neuromodulator, or prokinetic agents. Participants are randomized in a 1:1 ratio to either a 7-day vonoprazan-based PCAB test or to a reference strategy using esophagogastroduodenoscopy (EGD) plus 24-hour pH-impedance monitoring and high-resolution manometry in accordance with Lyon Consensus 2.0 and Rome IV criteria. The primary objective is to determine whether PCAB test-guided treatment is non-inferior to physiologic test-guided treatment with respect to clinical response, defined by improvement in reflux symptoms after 4 weeks of allocated therapy. Secondary objectives include: (1) assessment of the diagnostic performance of the PCAB test for pathologic acid reflux using 24-hour pH-impedance monitoring as the reference standard; (2) comparison of changes in Reflux Disease Questionnaire (RDQ) scores, Likert symptom scales for heartburn, regurgitation and chest pain, EQ-5D quality-of-life scores, symptom-free days, rescue antaciduse, and patient satisfaction; and (3) evaluation of treatment-emergent adverse events andserious adverse events. In the PCAB arm, vonoprazan 20 mg twice daily for 7 days constitutes the diagnostic test; PCAB responders and non-responders are then allocated to proton pump inhibitor (omeprazole-based) or neuromodulator (nortriptyline-based) regimens with matching placebos according to the underlying GERD phenotype (erosive esophagitis, non-erosive reflux disease,reflux hypersensitivity, or functional heartburn). In the physiologic-test arm, treatment selection (omeprazole versus nortriptyline, with placebos) is based directly on EGD and 24-hour pH-impedance findings and symptom association analysis. Outcomes are measured at multiple time points over 4 weeks using RDQ, symptom Likert scales, EQ-5D, symptom and antacid diaries, and standard safety assessments, and data will be analyzed primarily using non-inferiority methods for proportions and standard diagnostic accuracy metrics (sensitivity, specificity, predictive values, and likelihood ratios), with appropriate parametric ornon-parametric tests and longitudinal models.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
120
All participants in PCAB-test guided group will receive vonoprazan 20 mg orally twice daily for 7 days
Faculty of Medicine Siriraj Hospital, Mahidol University
Bangkok Noi, Bangkok, Thailand
Proportion of Participants with Clinical Response to Treatment
To compare the proportion of participants with typical gastroesophageal reflux disease (GERD) symptoms who achieve a clinical response to treatment. This will be compared between the group receiving treatment guided by the PCAB (Potassium-Competitive Acid Blocker) test and the group receiving treatment guided by physiological testing.
Time frame: 4 weeks
Diagnostic Performance of the PCAB Test for Pathologic Acid Reflux
To evaluate the diagnostic accuracy, sensitivity, and specificity of the PCAB test in identifying pathologic acid reflux. Upper gastrointestinal endoscopy (EGD) and physiological testing, interpreted according to the Lyon Consensus 2.0 criteria, will be used as the reference standard.
Time frame: Baseline
Change in GERD Symptom Severity (Likert Scale)
To compare treatment outcomes between the PCAB test-guided and physiological testing-guided groups using a Likert scale to assess the severity of heartburn, regurgitation, and chest pain. Subgroup analysis will be performed for erosive esophagitis, non-erosive reflux disease (NERD), reflux hypersensitivity, and functional heartburn.
Time frame: Baseline and at 4 weeks
Change in Reflux Disease Questionnaire (RDQ) Score
The Reflux Disease Questionnaire (RDQ) is a 12-item self-administered questionnaire assessing the frequency and severity of heartburn, regurgitation, and dyspeptic symptoms. Each item is scored from 0 to 5, and the overall RDQ score is calculated as the mean of the item scores, ranging from 0 to 5. Higher scores indicate more frequent and/or severe symptoms and therefore a worse outcome. The change in RDQ score from baseline to week 4 will be compared between the potassium-competitive acid blocker (P-CAB) test-guided group and the physiological testing-guided group. A greater reduction in the RDQ score indicates greater symptom improvement.
Time frame: Baseline and at 4 weeks
Percentage of Symptom-Free Days
To compare the percentage of 24-hour days without GERD symptoms between the two study arms over the 4-week study period.
Time frame: Up to 4 weeks
Frequency of Rescue Antacid Use
To compare the frequency of rescue antacid use and the percentage of 24-hour days without the need for rescue antacids between the two study arms.
Time frame: Up to 4 weeks
Change in Quality of Life (EQ-5D)
The EuroQol 5-Dimension 5-Level (EQ-5D-5L) questionnaire assesses health-related quality of life across five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has five response levels, ranging from no problems to extreme problems or inability to perform the activity. Responses will be converted into an EQ-5D-5L index score using the Thai value set. Index scores range from -0.4212 to 1.000, with 1.000 representing full health and scores below 0 representing health states considered worse than death. Higher scores indicate better health-related quality of life. Change will be calculated as the week 4 score minus the baseline score; a positive change indicates improvement. The change in index score will be compared between the P-CAB test-guided and physiological testing-guided groups.
Time frame: Baseline and at 4 weeks
Proportion of Participants Satisfied With the Assigned Treatment Protocol at Week 4
Overall treatment satisfaction will be assessed using a single-item 5-point Likert scale: 1 = very dissatisfied, 2 = dissatisfied, 3 = neither satisfied nor dissatisfied, 4 = satisfied, and 5 = very satisfied. Participants selecting a score of 4 or 5 will be classified as satisfied. The proportion of satisfied participants will be compared between the P-CAB test-guided and physiological testing-guided groups.
Time frame: At 4 weeks
Rate of Study Withdrawal Due to Severe Symptoms
To compare the number of participants in each arm who discontinue the study due to symptoms severely interfering with their daily life activities.
Time frame: Up to 4 weeks
Incidence of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
To assess and compare the safety profile, including the number of participants experiencing TEAEs and SAEs, between the PCAB test-guided treatment group and the physiological testing-guided treatment group.
Time frame: Up to 4 weeks
Participant Satisfaction With the Diagnostic Testing Method Assessed Using a Study-Specific 5-Point Likert Scale
Immediately after completing the assigned diagnostic procedure, participants will rate their overall satisfaction with the diagnostic testing method using a study-specific single-item 5-point Likert scale: 1 = very dissatisfied, 2 = dissatisfied, 3 = neither satisfied nor dissatisfied, 4 = satisfied, and 5 = very satisfied. Scores range from 1 to 5, with higher scores indicating greater satisfaction. Satisfaction scores will be compared between participants undergoing the P-CAB test and those undergoing physiological testing.
Time frame: Immediately after completion of diagnostic testing on Day 0
Prevalence of GERD Phenotypes
To determine the prevalence of erosive esophagitis, non-erosive reflux disease (NERD), reflux hypersensitivity, and functional heartburn among participants with typical GERD symptoms. Diagnosis and phenotyping will be established using 24-hour pH monitoring combined with EGD, according to the Lyon Consensus 2.0 criteria.
Time frame: Baseline
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