The Effects of High-dose Dual Therapy With Probiotics on Gut Microbiota for Helicobacter Pylori Rescue Treatment

The Effects of High-dose Dual Therapy Combined With Probiotics on Gut Microbiota for Helicobacter Pylori Rescue Treatment: A Prospective, Multicenter, Randomized Trial

The aim of this study was to evaluate the effects of High-dose Dual therapy combined with probiotics on the gut microbiota for Helicobacter pylori rescue treatment.

Study Overview

• Status: Completed
• Conditions: Metabolic Disturbance; Gut Microbiota; Helicobacter Pylori Eradication
• Intervention / Treatment: Drug: Amoxicillin; Drug: Bacillus subtilis enteric-coated capsules; Drug: Vonoprazan

Detailed Description

The combination of vonoprazan (VPZ) and amoxicillin (VA therapy) has been shown to achieve notable eradication rates for Helicobacter pylori (H. pylori). Patients who receive this treatment are prone to adverse reactions, such as diarrhea, abdominal distention. We plan to combine probiotic with the above treatment. However, it is not clear what changes in gut microbiota and metabolism may result from this therapy.

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Fujian
    • Xiamen, Fujian, China, 361015
      • Zhongshan Hospital (Xiamen), Fudan University

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age from 18 to 65 years;
• H.pylori infection diagnosed by 13C-urea breath test;
• A period of more than two months since the last eradication therapy for H. pylori;
• Patients who had previously failed 2 or more eradication regimens.

Exclusion Criteria:

• Allergy to any of the medications;
• Zollinger-Ellison syndrome, GC, Upper gastrointestinal bleeding, or Active peptic ulcer;
• Coexistence of significant concomitant illnesses, including heart disease, renal failure, hepatic disease, previous abdominal surgery, lactation, or pregnancy;
• Patients who had used probiotics, vonoprazan, and antibiotics in the past 12 weeks;
• Unwillingness to participate in this study.

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

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A; vonoprazan 20 mg bid + amoxicillin 0.75 g qid for 14 days, followed by 2 doses of bacillus subtilis enteric-coated capsules for 14 days.	Drug: Amoxicillin; Group A: vonoprazan 20 mg bid + amoxicillin 0.75 g qid for 14 days, followed by 2 doses of bacillus subtilis enteric-coated capsules for 14 days. Group B: vonoprazan 20 mg bid + amoxicillin 0.75 g qid+ 2 doses of bacillus subtilis enteric-coated capsules for 14 days. Group C: 2 doses of bacillus subtilis enteric-coated capsules for 14 days, followed by vonoprazan 20 mg bid + amoxicillin 0.75 g qid for 14 days. Group D: vonoprazan 20 mg bid + amoxicillin 0.75 g qid for 14 days.; Drug: Bacillus subtilis enteric-coated capsules; Group A: vonoprazan 20 mg bid + amoxicillin 0.75 g qid for 14 days, followed by 2 doses of bacillus subtilis enteric-coated capsules for 14 days. Group B: vonoprazan 20 mg bid + amoxicillin 0.75 g qid+ 2 doses of bacillus subtilis enteric-coated capsules for 14 days. Group C: 2 doses of bacillus subtilis enteric-coated capsules for 14 days, followed by vonoprazan 20 mg bid + amoxicillin 0.75 g qid for 14 days. Group D: vonoprazan 20 mg bid + amoxicillin 0.75 g qid for 14 days.; Drug: Vonoprazan; Group A: vonoprazan 20 mg bid + amoxicillin 0.75 g qid for 14 days, followed by 2 doses of bacillus subtilis enteric-coated capsules for 14 days. Group B: vonoprazan 20 mg bid + amoxicillin 0.75 g qid+ 2 doses of bacillus subtilis enteric-coated capsules for 14 days. Group C: 2 doses of bacillus subtilis enteric-coated capsules for 14 days, followed by vonoprazan 20 mg bid + amoxicillin 0.75 g qid for 14 days. Group D: vonoprazan 20 mg bid + amoxicillin 0.75 g qid for 14 days.
Experimental: Group B; vonoprazan 20 mg bid + amoxicillin 0.75 g qid+ 2 doses of bacillus subtilis enteric-coated capsules for 14 days.	Drug: Amoxicillin; Group A: vonoprazan 20 mg bid + amoxicillin 0.75 g qid for 14 days, followed by 2 doses of bacillus subtilis enteric-coated capsules for 14 days. Group B: vonoprazan 20 mg bid + amoxicillin 0.75 g qid+ 2 doses of bacillus subtilis enteric-coated capsules for 14 days. Group C: 2 doses of bacillus subtilis enteric-coated capsules for 14 days, followed by vonoprazan 20 mg bid + amoxicillin 0.75 g qid for 14 days. Group D: vonoprazan 20 mg bid + amoxicillin 0.75 g qid for 14 days.; Drug: Bacillus subtilis enteric-coated capsules; Group A: vonoprazan 20 mg bid + amoxicillin 0.75 g qid for 14 days, followed by 2 doses of bacillus subtilis enteric-coated capsules for 14 days. Group B: vonoprazan 20 mg bid + amoxicillin 0.75 g qid+ 2 doses of bacillus subtilis enteric-coated capsules for 14 days. Group C: 2 doses of bacillus subtilis enteric-coated capsules for 14 days, followed by vonoprazan 20 mg bid + amoxicillin 0.75 g qid for 14 days. Group D: vonoprazan 20 mg bid + amoxicillin 0.75 g qid for 14 days.; Drug: Vonoprazan; Group A: vonoprazan 20 mg bid + amoxicillin 0.75 g qid for 14 days, followed by 2 doses of bacillus subtilis enteric-coated capsules for 14 days. Group B: vonoprazan 20 mg bid + amoxicillin 0.75 g qid+ 2 doses of bacillus subtilis enteric-coated capsules for 14 days. Group C: 2 doses of bacillus subtilis enteric-coated capsules for 14 days, followed by vonoprazan 20 mg bid + amoxicillin 0.75 g qid for 14 days. Group D: vonoprazan 20 mg bid + amoxicillin 0.75 g qid for 14 days.
Experimental: Group C; 2 doses of bacillus subtilis enteric-coated capsules for 14 days, followed by vonoprazan 20 mg bid + amoxicillin 0.75 g qid for 14 days.	Drug: Amoxicillin; Group A: vonoprazan 20 mg bid + amoxicillin 0.75 g qid for 14 days, followed by 2 doses of bacillus subtilis enteric-coated capsules for 14 days. Group B: vonoprazan 20 mg bid + amoxicillin 0.75 g qid+ 2 doses of bacillus subtilis enteric-coated capsules for 14 days. Group C: 2 doses of bacillus subtilis enteric-coated capsules for 14 days, followed by vonoprazan 20 mg bid + amoxicillin 0.75 g qid for 14 days. Group D: vonoprazan 20 mg bid + amoxicillin 0.75 g qid for 14 days.; Drug: Bacillus subtilis enteric-coated capsules; Group A: vonoprazan 20 mg bid + amoxicillin 0.75 g qid for 14 days, followed by 2 doses of bacillus subtilis enteric-coated capsules for 14 days. Group B: vonoprazan 20 mg bid + amoxicillin 0.75 g qid+ 2 doses of bacillus subtilis enteric-coated capsules for 14 days. Group C: 2 doses of bacillus subtilis enteric-coated capsules for 14 days, followed by vonoprazan 20 mg bid + amoxicillin 0.75 g qid for 14 days. Group D: vonoprazan 20 mg bid + amoxicillin 0.75 g qid for 14 days.; Drug: Vonoprazan; Group A: vonoprazan 20 mg bid + amoxicillin 0.75 g qid for 14 days, followed by 2 doses of bacillus subtilis enteric-coated capsules for 14 days. Group B: vonoprazan 20 mg bid + amoxicillin 0.75 g qid+ 2 doses of bacillus subtilis enteric-coated capsules for 14 days. Group C: 2 doses of bacillus subtilis enteric-coated capsules for 14 days, followed by vonoprazan 20 mg bid + amoxicillin 0.75 g qid for 14 days. Group D: vonoprazan 20 mg bid + amoxicillin 0.75 g qid for 14 days.
Active Comparator: Group D; vonoprazan 20 mg bid + amoxicillin 0.75 g qid for 14 days.	Drug: Amoxicillin; Group A: vonoprazan 20 mg bid + amoxicillin 0.75 g qid for 14 days, followed by 2 doses of bacillus subtilis enteric-coated capsules for 14 days. Group B: vonoprazan 20 mg bid + amoxicillin 0.75 g qid+ 2 doses of bacillus subtilis enteric-coated capsules for 14 days. Group C: 2 doses of bacillus subtilis enteric-coated capsules for 14 days, followed by vonoprazan 20 mg bid + amoxicillin 0.75 g qid for 14 days. Group D: vonoprazan 20 mg bid + amoxicillin 0.75 g qid for 14 days.; Drug: Vonoprazan; Group A: vonoprazan 20 mg bid + amoxicillin 0.75 g qid for 14 days, followed by 2 doses of bacillus subtilis enteric-coated capsules for 14 days. Group B: vonoprazan 20 mg bid + amoxicillin 0.75 g qid+ 2 doses of bacillus subtilis enteric-coated capsules for 14 days. Group C: 2 doses of bacillus subtilis enteric-coated capsules for 14 days, followed by vonoprazan 20 mg bid + amoxicillin 0.75 g qid for 14 days. Group D: vonoprazan 20 mg bid + amoxicillin 0.75 g qid for 14 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gut Microbiota	Diversity and Compositional Analysis of Gut Microbiota is tested by Metagenomics.	day 0, day 44 (or 58), day 104 (or 118)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Eradication rate	Eradication rate of H pylori, presenting with negative results on the 13C-UBT test.	day 44 or day 58
Frequency of the adverse events	Incidence rate of the adverse events, including dyspepsia, nausea, vomiting, abdominal pain, bloating, diarrhea, dizziness, headache, skin rash, fatigue and fever.	day 44 or day 58
Compliance rate of the drugs	Compliance is defined as good when they had taken more than 80% of the total medication.	day 44 or day 58
Fecal Metabolites	Fecal metabolites is tested by Gas Chromatography-Mass Spectrometry Analysis.	day 0, day 44 (or 58), day 104 (or 118)
Small intestinal bacterial overgrowth	Small intestinal bacterial overgrowth is tested by Hydrogen-Methane Breath.	day 0, day 44 (or 58), day 104 (or 118)

Collaborators and Investigators

• Sponsor: Zhongshan Hospital (Xiamen), Fudan University
• Investigators: Principal Investigator: Yucheng Zhu, Ph.D., Zhongshan Hospital (Xiamen), Fudan University

Publications and helpful links

General Publications

• Hu Y, Xu X, Ouyang YB, He C, Li NS, Xie C, Peng C, Zhu ZH, Shu X, Xie Y, Lu NH, Zhu Y. Altered Gut Microbiota and Short-Chain Fatty Acids After Vonoprazan-Amoxicillin Dual Therapy for Helicobacter pylori Eradication. Front Cell Infect Microbiol. 2022 Jun 2;12:881968. doi: 10.3389/fcimb.2022.881968. eCollection 2022.

Study record dates

Study Major Dates

• Study Start (Actual): January 31, 2024
• Primary Completion (Actual): December 30, 2024
• Study Completion (Actual): February 28, 2025

Study Registration Dates

• First Submitted: February 19, 2024
• First Submitted That Met QC Criteria: March 4, 2024
• First Posted (Actual): March 5, 2024

Study Record Updates

• Last Update Posted (Actual): May 13, 2025
• Last Update Submitted That Met QC Criteria: May 10, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Helicobacter pylori; Eradication; Gut microbiota; Amoxicillin; Vonoprazan
• Additional Relevant MeSH Terms: Anti-Bacterial Agents; Anti-Infective Agents; Amoxicillin
• Other Study ID Numbers: ZYC-Hp2024

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: We may balance the potential benefits and risks for each request and then provide the data that could be shared.
• IPD Sharing Time Frame: The data will be available once the results have been uploaded in the PRS system and will be available for 2 years.
• IPD Sharing Access Criteria: Emails could be sent to the emails below to obtain the shared data: zhu.yucheng@zsxmhospital.com; li.keng@zsxmhospital.com
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No