Comparison of the Efficacies of Two Novel Dose Dual Therapies in the First-line Helicobacter Pylori Eradication (Helicobacter)

Background:

The key factors for success are the maintenance of intragastric pH > 6 and the drug resistance to antibiotics. Proton pump inhibitor (PPI)-based high-dose dual therapy is a novel anti-Helicobacter pylori (H. pylori) treatment. According to the investigators' previous study, the Esomeprazole-based high-dose dual therapy can achieve a higher eradication rate than standard triple therapy. The main reason for the high eradication rate was the use of high-dose esomeprazole which maintained 24-hour high intra-gastric pH. Another important reason was that investigators used only one antibiotic (Amoxicillin) with very low antibiotic resistance rates (0-2%). As compared to quadruple concomitant therapy which uses 3 antibiotics (clarithromycin, amoxicillin, and metronidazole), concomitant therapy could induce drug resistance which could affect public health issues.

Vonoprazan is a new gastric acid suppression agent, classified as a potassium-competitive acid blocker (PCAB). Its acid inhibition efficacy is superior to that of PPI. It has been evidenced that 7-day vonoprazan-based triple therapy achieved a higher eradication rate than 7-day PPI-based triple therapy in the first-line treatment of H. pylori infection but vonoprazan-based high-dose dual therapy can achieve a higher eradication rate than PPI-based thigh-dose dual therapy remains unclear.

Aims: (1) To test whether the efficacies of 14-day PCAB-based high-dose dual therapy can achieve a higher eradication rate than 14-day PPI-based high-dose dual therapy in the first-line treatment of H. pylori infection, (2) to examine the impacts of antibiotic resistance of H. pylori on the eradication efficacies of these two high-dose dual anti- H. pylori treatments.

Methods: The investigators will recruit 300 adult participants with H. pylori infection from Kaohsiung Chang Gung Memorial Hospital. Using a computer-generated randomized sequence, the investigators randomly allocated 150 patients to either 14-day high-dose dual therapy (vonoprazan 20 mg bid, and amoxicillin 750mg qid. for 14 days) or 150 patients (Esomeprezole 40 mg tid, and amoxicillin 750mg qid. for 14 days). Participants are asked to return in the second week to assess drug compliance and adverse events. Post-treatment H. pylori status is assessed by a 13C-urea breath test at week 8. Additionally, antibiotic susceptibility of H. pylori will be examined. Finally, the rates of eradication, adverse events and compliance will be compared between two groups by chi-square test, and the host and bacterial factors influencing each efficacy of the regimen are assessed by multivariate analysis.

Expected results: The acid inhibition efficacy of PCAB is superior to that of PPI. The investigators expect the PCAB-based high-dose dual therapy can achieve a better H. pylori eradication rate the PPA-based high-dose dual therapy. Minor adverse effects can be expected in each group of participants.

Study Overview

• Status: Enrolling by invitation
• Conditions: HELICOBACTER PYLORI INFECTIONS
• Intervention / Treatment: Drug: Vonoprazan; Drug: Amoxicillin; Drug: Esomeprazole 40mg

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Phase 3

Contacts and Locations

Study Locations

• Taiwan
  • Others
    • Kaohsiung, Others, Taiwan, 833
      • Kaohsiung Chang Gung Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. At least 20 years of age, with endoscopically proven peptic ulcer diseases or gastritis are prospectively recruited for this pilot study

Exclusion Criteria:

1. Previous H. pylori-eradication therapy,
2. Ingestion of antibiotics, bismuth, or PPIs within the prior 4 weeks,
3. Patients with an allergic history to the medications used,
4. Patients with previous gastric surgery,
5. The coexistence of serious concomitant illness (for example, decompensated liver cirrhosis, uremia),
6. Pregnant women.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 14-day PCAB-based high-dose dual therapy.; vonoprazan 20 mg bid, and amoxicillin 750mg qid. for 14 days	Drug: Vonoprazan; Vonoprazan (20 mg bid, for 14 days); Drug: Amoxicillin; Amoxicillin (750 mg qid, for 14 days)
Experimental: 14-day PPI-Based High-Dose Dual Therapies; Esomeprezole 40 mg tid, and amoxicillin 750mg qid. for 14 days	Drug: Amoxicillin; Amoxicillin (750 mg qid, for 14 days); Drug: Esomeprazole 40mg; Esomeprazole (40 mg tid, for 14 days)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Participants With Eradication of H. pylori Confirmed by Urea Breath Test (UBT)	Description: This outcome will measure the percentage of participants in each treatment group (PCAB-based dual therapy and PPI-based dual therapy) who achieve H. pylori eradication.; Definition of Eradication: Eradication is defined as a negative result on the Urea Breath Test (UBT).; Calculation Method: The proportion of eradicated participants will be calculated as: (Number of participants with confirmed eradication by UBT) / (Total participants analyzed)×100%	6 to 8 weeks after the completion of the 14-day treatment period.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Association Between Antibiotic Resistance and H. pylori Eradication Rate	Description: This outcome will evaluate whether pre-treatment antibiotic resistance (e.g., amoxicillin resistance) is associated with the eradication success rate of PCAB-based and PPI-based high-dose dual therapies.; Statistical Analysis: The correlation between antibiotic resistance status (resistant vs. susceptible) and eradication outcome (eradicated vs. not eradicated) will be analyzed using appropriate logistic regression models or chi-square tests.	esistance testing at baseline, and eradication confirmation at 6 to 8 weeks post-treatment.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Antibiotic Resistance Profile of H. pylori Prior to Treatment	Description: This outcome will assess the pre-treatment antibiotic resistance of H. pylori strains collected from participants.; Resistance Measurement: Resistance to amoxicillin and other relevant antibiotics will be determined through bacterial culture and susceptibility testing (e.g., MIC values in μg/mL or resistant/susceptible categories).	Baseline (prior to treatment initiation).

Collaborators and Investigators

• Sponsor: Chang Gung Memorial Hospital

Publications and helpful links

General Publications

• Liu L, Shi H, Shi Y, Wang A, Guo N, Li F, Nahata MC. Vonoprazan-based therapies versus PPI-based therapies in patients with H. pylori infection: Systematic review and meta-analyses of randomized controlled trials. Helicobacter. 2024 May-Jun;29(3):e13094. doi: 10.1111/hel.13094.
• Gotoda T, Kusano C, Suzuki S, Horii T, Ichijima R, Ikehara H. Clinical impact of vonoprazan-based dual therapy with amoxicillin for H. pylori infection in a treatment-naive cohort of junior high school students in Japan. J Gastroenterol. 2020 Oct;55(10):969-976. doi: 10.1007/s00535-020-01709-4. Epub 2020 Jul 14.

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2025
• Primary Completion (Estimated): February 28, 2025
• Study Completion (Estimated): February 28, 2025

Study Registration Dates

• First Submitted: November 19, 2024
• First Submitted That Met QC Criteria: February 2, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 9, 2025
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Helicobacter pylori; Proton pump inhibitors; High-dose dual therapy; Potassium-competitive acid blocker; Antibiotic susceptibility
• Additional Relevant MeSH Terms: Anti-Bacterial Agents; Anti-Infective Agents; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents; Enzyme Inhibitors; Anti-Ulcer Agents; Proton Pump Inhibitors; Amoxicillin; Esomeprazole
• Other Study ID Numbers: IRB 202200416A3; CMRPG8M1121 (Other Grant/Funding Number: Chang Gung Memorial Hospital)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There are no plans to share individual participant data (IPD) from this study. The data include sensitive information that may compromise participant privacy, even if de-identified. Ethical considerations and privacy regulations prevent data sharing.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No