Potassium Competitive Acid Blocker (PCAB) Test-Guided vs Physiologic Test-Guided Treatment in Patients With Typical Reflux Symptoms

July 15, 2026 updated by: Mahidol University

Potassium Competitive Acid Blocker (PCAB) Test-Guided vs Physiologic Test-Guided Treatment in Patients With Typical Reflux Symptoms: A Randomized Non-inferiority Trial

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

Study Overview

Status

Enrolling by invitation

Conditions

Intervention / Treatment

Detailed Description

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

Enrollment (Estimated)

120

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Thailand
    • Bangkok
      • Bangkok Noi, Bangkok, Thailand, 10700
        • Faculty of Medicine Siriraj Hospital, Mahidol University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Age between 18 and 70 years.
  • Presence of specific gastroesophageal reflux disease (GERD) symptoms, including heartburn, regurgitation, and/or esophageal chest pain, occurring at least 4 times per week for more than 4 weeks prior to enrollment.

Exclusion Criteria:

  • Presence of GERD complications, including esophageal stricture and/or Barrett's esophagus.
  • Concomitant symptoms that may interfere with GERD treatment, such as frequent belching or rumination syndrome.
  • History of gastric or duodenal ulcers.
  • History of upper gastrointestinal surgery (involving the esophagus, stomach, or small intestine).
  • Use of any of the following medications within 4 weeks prior to enrollment: aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), mucoprotective agents, prokinetics, or neuromodulators.
  • Use of proton pump inhibitors (PPIs), histamine H2-receptor antagonists (H2RAs), or potassium-competitive acid blockers (PCABs) within 2 weeks prior to enrollment. (Note: Patients may become eligible if they complete a minimum 2-week washout period).
  • Any contraindications for ambulatory esophageal reflux monitoring.
  • Known history of hypersensitivity, allergy, or adverse reactions to the study medications: vonoprazan, omeprazole, or nortriptyline.
  • Pregnant or breastfeeding women.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: PCAB-test guided
All patients assigned in PCAB-test guide group will receive esophagodeuodenoscopy, 24-hr pH and impedance monitoring then Vonoprazan 20 mg orally twice daily was prescribed for 7 days.
Diagnostic test: PCAB-test guided
All participants in PCAB-test guided group will receive vonoprazan 20 mg orally twice daily for 7 days
No Intervention: Physiologic-test guided
All patients assigned in Physiologic-test guided group will receive esophagodeuodenoscopy, 24-hr pH and impedance monitoring.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of Participants with Clinical Response to Treatment
Time Frame: 4 weeks
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.
4 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Diagnostic Performance of the PCAB Test for Pathologic Acid Reflux
Time Frame: Baseline
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.
Baseline
Change in GERD Symptom Severity (Likert Scale)
Time Frame: Baseline and at 4 weeks
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.
Baseline and at 4 weeks
Change in Reflux Disease Questionnaire (RDQ) Score
Time Frame: Baseline and at 4 weeks

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.
Baseline and at 4 weeks
Percentage of Symptom-Free Days
Time Frame: Up to 4 weeks
To compare the percentage of 24-hour days without GERD symptoms between the two study arms over the 4-week study period.
Up to 4 weeks
Frequency of Rescue Antacid Use
Time Frame: Up to 4 weeks
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.
Up to 4 weeks
Change in Quality of Life (EQ-5D)
Time Frame: Baseline and at 4 weeks

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.
Baseline and at 4 weeks
Proportion of Participants Satisfied With the Assigned Treatment Protocol at Week 4
Time Frame: At 4 weeks
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.
At 4 weeks
Rate of Study Withdrawal Due to Severe Symptoms
Time Frame: Up to 4 weeks
To compare the number of participants in each arm who discontinue the study due to symptoms severely interfering with their daily life activities.
Up to 4 weeks
Incidence of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time Frame: Up to 4 weeks
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.
Up to 4 weeks
Participant Satisfaction With the Diagnostic Testing Method Assessed Using a Study-Specific 5-Point Likert Scale
Time Frame: Immediately after completion of diagnostic testing on Day 0
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.
Immediately after completion of diagnostic testing on Day 0
Prevalence of GERD Phenotypes
Time Frame: Baseline
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.
Baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mahidol University

Investigators

  • Principal Investigator: Monthira Maneerattanaporn, MD, Mahidol University
  • Study Chair: Somchai Leelakusolvong, MD, Mahidol University
  • Study Chair: Tanawat Geeratragool, MD, Mahidol University
  • Study Chair: Siwakan Phuetphaichit, MD, Mahidol University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 18, 2026

Primary Completion (Estimated)

March 1, 2027

Study Completion (Estimated)

March 1, 2027

Study Registration Dates

First Submitted

June 21, 2026

First Submitted That Met QC Criteria

July 15, 2026

First Posted (Actual)

July 16, 2026

Study Record Updates

Last Update Posted (Actual)

July 16, 2026

Last Update Submitted That Met QC Criteria

July 15, 2026

Last Verified

July 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Si 057/2026

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

To protect participant confidentiality and comply with institutional and regulatory requirements, no IPD will be shared unless with reasonable request.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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