Fourteen-Day Vonoprazan-Based Dual Therapy With Amoxicillin as First-Line Helicobacter Pylori Treatment in Comparison With Extended Sequential Therapy

Fourteen-Day Vonoprazan-Based Dual Therapy With Amoxicillin as First-Line Helicobacter Pylori Treatment in Comparison With Extended Sequential Therapy: A Randomized Controlled Trial in Taiwan

Background：Helicobacter pylori infection is a well-established risk factor for peptic ulcer disease and gastric cancer. It's now a consensus of experts that H.pylori infection should be treated once it is recognized. Extended proton pump inhibitor (PPI)-based sequential therapy as one of the most commonly used first-line regimens provides a satisfactory eradication rate of 90.7% (95% CI, 87.4% - 94.0%). Nevertheless, its complexity of the "sequential" usage is sometimes confusing to the patients and may lead to treatment failure. The emerging new regimen - vonoprazan-based dual therapy, on the other hand, is another appealing choice with simplicity, and low pill burden. However, there's still no evidence regarding the use of vonoprazan-based dual therapy with high-dose amoxicillin (1000mg twice daily) as the first-line regimen in Taiwan. This study aimed to compare the efficacy of the current standard first-line regimen, sequential therapy, with that of vonoprazan-based dual therapy with high-dose Amoxicillin.

Objectives: To compare the efficacy of the current standard first-line regimen, sequential therapy, with that of vonoprazan-based dual therapy, through a randomized controlled trial.

Methods: Patients with H.pylori infection who was over 20 years old and agree to participate in the trial will be recruited. Those who had received H.pylori eradication before, are known to be allergic to any drug used in this trial, are pregnant, or refuse to participate in the trial for any reason will be excluded. We then allocate these patients into two groups randomly - one group receiving vonoprazan-based dual therapy with high-dose amoxicillin (vonoprazan 20 mg + amoxicillin 1000 mg twice daily for fourteen days) and the other receiving extended sequential therapy (lansoprazole 30mg plus amoxicillin 1000mg twice daily for 7 days, followed by lansoprazole 30mg, clarithromycin 500mg, and metronidzole 500mg twice daily for an additional 7 days). Eradication success was evaluated by 13C-urea breath test at least 4 weeks after treatment.

Outcome analysis: The study will be designed as a non-inferiority trial. We anticipate that the two regimens will have comparable efficacy. Besides, we'll also design a questionnaire to evaluate the adverse effects, whether they took the drugs in the right way, and patient's satisfaction of the drug regimen. The vonoprazan dual therapy with high-dose amoxicillin will be anticipated to have fewer adverse effects, better compliance, and better satisfaction.

Study Overview

• Status: Recruiting
• Conditions: Helicobacter Pylori Infection
• Intervention / Treatment: Drug: Vonoprazan and Amoxicillin; Drug: Lansoprazole, Amoxicillin, Clarithromycin and Metronidazole

Detailed Description

Background：Helicobacter pylori infection is a well-established risk factor for peptic ulcer disease and gastric cancer. It's now a consensus of experts that H.pylori infection should be treated once it is recognized. Extended proton pump inhibitor (PPI)-based sequential therapy as one of the most commonly used first-line regimens provides a satisfactory eradication rate of 90.7% (95% CI, 87.4% - 94.0%). Nevertheless, its complexity of the "sequential" usage is sometimes confusing to the patients and may lead to treatment failure. The emerging new regimen - vonoprazan-based dual therapy, on the other hand, is another appealing choice with simplicity, and low pill burden. However, there's still no evidence regarding the use of vonoprazan-based dual therapy with high-dose amoxicillin (1000mg twice daily) as the first-line regimen in Taiwan. This study aimed to compare the efficacy of the current standard first-line regimen, sequential therapy, with that of vonoprazan-based dual therapy with high-dose Amoxicillin.

Objectives: To compare the efficacy of the current standard first-line regimen, sequential therapy, with that of vonoprazan-based dual therapy, through a randomized controlled trial.

Methods: Patients with H.pylori infection who was over 20 years old and agree to participate in the trial will be recruited. Those who had received H.pylori eradication before, are known to be allergic to any drug used in this trial, are pregnant, or refuse to participate in the trial for any reason will be excluded. We then allocate these patients into two groups randomly - one group receiving vonoprazan-based dual therapy with high-dose amoxicillin (vonoprazan 20 mg + amoxicillin 1000 mg twice daily for fourteen days) and the other receiving extended sequential therapy (lansoprazole 30mg plus amoxicillin 1000mg twice daily for 7 days, followed by lansoprazole 30mg, clarithromycin 500mg, and metronidzole 500mg twice daily for an additional 7 days). Eradication success was evaluated by 13C-urea breath test at least 4 weeks after treatment.

Outcome analysis: The study will be designed as a non-inferiority trial. We anticipate that the two regimens will have comparable efficacy. Besides, we'll also design a questionnaire to evaluate the adverse effects, whether they took the drugs in the right way, and patient's satisfaction of the drug regimen. The vonoprazan dual therapy with high-dose amoxicillin will be anticipated to have fewer adverse effects, better compliance, and better satisfaction.

• Study Type: Interventional
• Enrollment (Estimated): 318
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Te-Ling Ma, MD; Phone Number: 886905301798; Email: martin1985831@gmail.com

Study Locations

• Taiwan
  • New Taipei City, Taiwan, 24352
    • Recruiting
    • Fu Jen Catholic University Hospital, Fu Jen Catholic University
    • Contact: Te-Ling Ma, M.D.; Phone Number: 0905301798; Email: martin1985831@gmail.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Patients with naive H. pylori infection
2. Subjects with over 20 years old

Exclusion Criteria:

1. Younger than 20 years old
2. Ever received H. eradication therapy
3. ever received total or subtotal gastrectomy in the past
4. Severe chronic disease, such as end stage renal disease, liver cirrhosis, incurable malignant tumors
5. Women who are pregnant or breastfeeding
6. Those who are not suitable to receive study drugs: such as a history of allergies to study drugs or serious side effects, etc.
7. Patient with estimated glomerular filtration rate (eGFR) less than 60 ml/min/1.73 mt2

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
Experimental: VA14; Vonoprazan-Amoxicillin Dual Therapy for 14days	Drug: Vonoprazan and Amoxicillin; vonoprazan 20 mg and amoxicillin 1000 mg b.i.d. PC for 14days
Active Comparator: S14; Sequential therapy for 14 days	Drug: Lansoprazole, Amoxicillin, Clarithromycin and Metronidazole; lansoprazole 30 mg + amoxicillin 1000 mg b.i.d. AC for 7 days, followed by the same PPI + clarithromycin 500 mg + metronidazole 500 mg b.i.d. AC for 7 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
primary outcome is the eradication rate in the first-line treatment	At least 6 weeks after the end of treatment, the carbon 13-breath test will be used to evaluate whether the eradication is successful. The eradication rate in each group will be presented as "%	Up to 8-12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The secondary outcomes are the compliance, frequency of adverse events	After eradication treatment, participants will go back to the outpatients clinics to evaluate whether they take all of or > 80% drugs. The investigators will also record any side effect associated with treatment, such as skin rash, dizziness, headache, taste distortion, and etc. The severity grading include "none", "mild", "moderate"	Up to 8-12 weeks

Collaborators and Investigators

• Sponsor: Fu Jen Catholic University Hospital
• Investigators: Study Chair: Chi-Yang Chang, PhD, Fu Jen Catholic University Hospital, Taiwan

Study record dates

Study Major Dates

• Study Start (Actual): November 14, 2023
• Primary Completion (Estimated): June 30, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: November 12, 2023
• First Submitted That Met QC Criteria: December 3, 2023
• First Posted (Estimated): December 5, 2023

Study Record Updates

• Last Update Posted (Estimated): December 5, 2023
• Last Update Submitted That Met QC Criteria: December 3, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Bacterial Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Protein Synthesis Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Metronidazole; Dexlansoprazole; Lansoprazole; Amoxicillin; Clarithromycin
• Other Study ID Numbers: FJUH112288

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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