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

Official title

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

Overview

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

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.

Interventions

• Diagnostic test PCAB-test guided
  All participants in PCAB-test guided group will receive vonoprazan 20 mg orally twice daily for 7 days

Primary outcome measures

• Proportion of Participants with Clinical Response to Treatment [Time frame: 4 weeks]

Secondary outcome measures (11)

• Diagnostic Performance of the PCAB Test for Pathologic Acid Reflux [Time frame: Baseline]
• Change in GERD Symptom Severity (Likert Scale) [Time frame: Baseline and at 4 weeks]
• Change in Reflux Disease Questionnaire (RDQ) Score [Time frame: Baseline and at 4 weeks]
• Percentage of Symptom-Free Days [Time frame: Up to 4 weeks]
• Frequency of Rescue Antacid Use [Time frame: Up to 4 weeks]
• Change in Quality of Life (EQ-5D) [Time frame: Baseline and at 4 weeks]
• Proportion of Participants Satisfied With the Assigned Treatment Protocol at Week 4 [Time frame: At 4 weeks]
• Rate of Study Withdrawal Due to Severe Symptoms [Time frame: Up to 4 weeks]
• Incidence of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [Time frame: 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]
• Prevalence of GERD Phenotypes [Time frame: Baseline]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

Thailand · 1 center

• Faculty of Medicine Siriraj Hospital, Mahidol University — Bangkok Noi

Publications

• Nasseri-Moghaddam S, Razjouyan H, Nouraei M, Alimohammadi M, Mamarabadi M, Vahedi H, Pourshams A, Mohamadnejad M, Zamani F, Sadr F, Darvish-Moghaddam S, Farsi P, Malekzadeh R. Inter- and intra-observer variability of the Los Angeles classification: a reassessment. Arch Iran Med. 2007 Jan;10(1):48-53. PMID 17198454
• Dong P, Lin L, Sun K, Tang F, Li Q, Zhou X, Liu F, Yang Z, Li J, Jiang L, Zhao P, Sun X, Wang Q. Accuracy of the diagnosis of gastroesophageal reflux disease by a trial of potassium-competitive acid blocker treatment. BMC Gastroenterol. 2025 May 26;25(1):406. doi: 10.1186/s12876-025-03981-1. PMID 40419956
• Dickman R, Maradey-Romero C, Fass R. The role of pain modulators in esophageal disorders - no pain no gain. Neurogastroenterol Motil. 2014 May;26(5):603-10. doi: 10.1111/nmo.12339. PMID 24750261
• Shah ED, Gyawali CP, Chan WW. Optimizing the Cost-Effective Evaluation of Gastroesophageal Reflux by Typical Symptom Phenotypes After Failure of Empiric Acid Suppression Trial. Am J Gastroenterol. 2026 Mar 1;121(3):635-648. doi: 10.14309/ajg.0000000000003576. Epub 2025 Jun 5. PMID 40471840
• Otake K, Sakurai Y, Nishida H, Fukui H, Tagawa Y, Yamasaki H, Karashima M, Otsuka K, Inatomi N. Characteristics of the Novel Potassium-Competitive Acid Blocker Vonoprazan Fumarate (TAK-438). Adv Ther. 2016 Jul;33(7):1140-57. doi: 10.1007/s12325-016-0345-2. Epub 2016 Jun 10. PMID 27287852
• Oshima T, Miwa H. Potent Potassium-competitive Acid Blockers: A New Era for the Treatment of Acid-related Diseases. J Neurogastroenterol Motil. 2018 Jul 30;24(3):334-344. doi: 10.5056/jnm18029. PMID 29739175
• Rawla P, Sunkara T, Ofosu A, Gaduputi V. Potassium-competitive acid blockers - are they the next generation of proton pump inhibitors? World J Gastrointest Pharmacol Ther. 2018 Dec 13;9(7):63-68. doi: 10.4292/wjgpt.v9.i7.63. PMID 30595950
• Numans ME, Lau J, de Wit NJ, Bonis PA. Short-term treatment with proton-pump inhibitors as a test for gastroesophageal reflux disease: a meta-analysis of diagnostic test characteristics. Ann Intern Med. 2004 Apr 6;140(7):518-27. doi: 10.7326/0003-4819-140-7-200404060-00011. PMID 15068979

Identifiers

NCT: NCT07707011 · Si 057/2026

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗