A Phase 3 interventional study of Bismuth quadruple therapy with optimized PPI and Bismuth quadruple therapy with standard PPI in Helicobacter Pylori, sponsored by VA Office of Research and Development. Not yet recruiting at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-08-04.
Sponsored by VA Office of Research and Development · Phase 3, Interventional, and Treatment
The primary objective of this study is to compare the Helicobacter pylori (H. pylori) eradication rate following empiric bismuth-based quadruple therapy (BQT) versus a personalized H. pylori treatment strategy in treatment-naïve Veterans with confirmed H. pylori infection.
This study is an eight-week, parallel two-arm, double-blinded, prospective, single-site randomized clinical trial designed to test the hypothesis that personalized H. pylori therapy achieves higher eradication rates compared to the standard empiric BQT regimen. Secondary outcomes include comparisons of treatment adherence, tolerability, and the incidence of treatment-related side effects and adverse events between the two groups. A total of 360 treatment-naïve Veterans with active H. pylori infection, confirmed by a positive H. pylori stool antigen test (HPsAg), will be enrolled, randomized, and analyzed at the VA San Diego Healthcare System (VASDHS). Participants who meet eligibility criteria and provide informed consent will be randomized in a 1:1 ratio to receive either a 14-day personalized H. pylori treatment regimen (n=180) or a standard 14-day empiric BQT regimen (n=180).
Participants randomized to personalized therapy will receive H. pylori treatment that incorporates 1) standard or optimized proton pump inhibitor (PPI) dosing according to participants' CYP2C19 metabolizer phenotype, and 2) tailored antibiotics according to participants' noninvasive (stool) H. pylori antibiotic susceptibility testing (AST). All participants will complete a baseline questionnaire and provide pre-treatment stool and blood samples for H. pylori AST and serum CYP2C19 testing, respectively. Follow-up will include brief telephone interviews during week 1 and week 2 of treatment and again two weeks post-treatment to assess adherence and monitor for adverse events. Cure will be assessed using a post-treatment stool antigen test (HPsAg) at week 8 (four weeks after completing therapy).
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Exclusion Criteria:
The investigators will exclude individuals with:
Participants allocated to the experimental group receive a personalized treatment based on clarithromycin (CLR) and amoxicillin susceptibility and CYP2C19 metabolizer profile status as follows: 1. CLR or amoxicillin resistant/CYP2C19 normal/rapid/ultrarapid metabolizers receive bismuth quadruple therapy (BQT) with optimized PPI (bismuth 524mg QID, metronidazole 500mg QID, tetracycline 500MG QID, and omeprazole 20 mg QID) for 14 days. 2. CLR or amoxicillin resistant/CYP2C19 intermediate/poor metabolizers receive BQT with standard PPI (BQT + omeprazole 20mg BID) for 14 days. 3. CLR and amoxicillin susceptible/CYP2C19 normal/rapid/ultrarapid metabolizers receive CLR triple therapy with optimized PPI (amoxicillin 1000mg BID, clarithromycin 500mg BID, and omeprazole 20mg QID) for 14 days. 4. CLR and amoxicillin susceptible/CYP2C19 intermediate/poor metabolizers receive CLR triple therapy with standard PPI (CLR triple therapy + omeprazole 20mg BID).
Drug: Bismuth quadruple therapy with optimized PPI · Drug: Bismuth quadruple therapy with standard PPI · Drug: Clarithromycin triple therapy with optimized PPI · Drug: Clarithromycin triple therapy with standard PPI
Participants allocated to this group receive standard bismuth-based quadruple therapy (BQT), which is first-line treatment according to US clinical guidelines. BQT consists of bismuth subsalicylate 524mg QID (or bismuth subcitrate if salicylate allergy), tetracycline 500mg QID, metronidazole 500mg QID, and twice daily standard dose PPI (omeprazole 20mg BID) for 14 days.
Drug: Standard bismuth quadruple therapy
Bismuth 524mg QID, Metronidazole 500mg QID, Tetracycline 500MG QID, and Omeprazole 20 mg QID for 14 days.
Bismuth 524mg QID, Metronidazole 500mg QID, Tetracycline 500mg QID, and Omeprazole 20mg (active BID + placebo BID) for 14 days. \*\*NOTE: placebo tablets are used to maintain the same number of pills in all study arms and preserve blinding
Amoxicillin 1000mg (active BID + placebo BID), Clarithromycin 500mg (active BID + placebo BID), and Omeprazole 20mg QID for 14 days. \*\*NOTE: placebo tablets are used to maintain the same number of pills in all study arms and preserve blinding
Amoxicillin 1000mg (active BID + placebo BID), Clarithromycin 500mg (active BID + placebo BID), and Omeprazole 20mg (active BID + placebo BID) for 14 days. \*\*NOTE: placebo tablets are used to maintain the same number of pills in all study arms and preserve blinding
Bismuth 524mg QID, Metronidazole 500mg QID, Tetracycline 500mg QID, and Omeprazole 20mg (active BID + placebo BID) for 14 days. \*\*NOTE: placebo tablets are used to maintain the same number of pills in all study arms and preserve blinding
H. pylori eradication success
The primary outcome is H. pylori eradication success, defined as negative post-treatment H. pylori stool antigen (HPsAg) testing. Post-treatment persistent positive HPsAg indicates eradication treatment failure; equivocal tests will be conservatively counted as a treatment failure, along with participants who fail to complete follow up testing within the prespecified timeframe (intention-to-treat analysis). All participants must be off proton pump inhibitors (PPIs) for a minimum of 2 weeks, and off antibiotics or bismuth for at least 4 weeks prior to HPsAg testing. HPsAg testing will be performed between 4-6 weeks post-treatment.
Time frame: 4-6 weeks after treatment
Treatment adherence
Patient-reported treatment adherence will be evaluated using the validated Adherence to Refills and Medications Scale (ARMS) and pill counts obtained during telephone interviews conducted in weeks 1 and 2 following treatment initiation. Adherence will be defined as \>90% of the treatment regimen consumed.
Time frame: Weeks 1 and 2 after treatment initiation
Treatment-emergent side effects/adverse events
Participant-reported side effects and adverse events will be collected during telephone interviews conducted in weeks 1 and 2 following treatment initiation, and in week 6 following treatment completion. Treatment-emergent adverse events will be classified using the Medical Dictionary for Regulatory Activities terminology (MedDRA).
Time frame: Weeks 1 and 2 after treatment initiation, 6 weeks after treatment completion
Plan to share: No
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