Second Line Bismuth Containing Quadruple Therapy With Supplementary Probiotic

The Effect of Supplementary Probiotic in the Dysbiosis of Gut Microbiota Caused by Second Line Bismuth Containing Quadruple Therapy in Helicobacter Pylori Eradication- A Multicentered, Randomized Double Blind Placebo-controlled Trial

This study is designed to evaluate the clinical outcome of second line Bismuth containing quadruple therapy with supplementary probiotic for Helicobacter pylori eradication

Study Overview

• Status: Recruiting
• Conditions: H.Pylori Gastrointestinal Disease
• Intervention / Treatment: Dietary supplement: Probiotics packets; Dietary supplement: Placebo packets

Detailed Description

The role of Helicobacter pylori infection in the development of peptic ulcer disease and gastric cancer have been studied extensively. Eradication of H. pylori decreases the incidence of peptic ulcer and also gastric cancer. First line therapies for H. pylori eradication with PPI and antibiotic combinations considering local clarithromycin resistant rate reaching successful rates above 90%. Bismuth containing quadruple therapy (BQT), as a major choice of second line therapy, is widely prescribed but with considerable gastrointestinal side effects including diarrhea, nausea, vomiting, bloating and abdominal pain. Probiotics supplementation is defined as the adding of non-pathologic living microorgnisms. Numerous recent studies including meta-analyses and several randomized control trials revealed supplementary probiotics may improve the adverse effects and increase the successful rate of eradication therapy. Therefore, this study aim to assess the clinical impact of probiotics on Bismuth therapy and eradication of H. pylori.

It's a multicentered, randomized double blind placebo-controlled trial to evaluate the clinical outcome of second line Bismuth containing quadruple therapy with supplementary probiotic for Helicobacter pylori eradication. During the study, expected 200 patients failing in first-line Bismuth therapy would be enrolled in the trial. 200 patients are divided into two groups: one group receive probiotic for treatment period and the other group receive placebo. The treatment period is designed for 56 days: Bismuth containing quadruple therapy is performed from day 1~10 and probiotic (or placebo) is taken from day 1~56.

There are 5 visits for subjects to follow: day 0, day 10, day 56, 1 year and 3 years(optional). Esophagogastroduodenal scope for the pathology, H. pylori culture, susceptibility testing, genotypic resistance and virulence factors before D0. 13C-Urea breath tests are used to check Helicobacter pylori eradication on day 56, 1 year and 3 year. In addition to blood samples for general tests, stool samples would be collected on every visit to analyze gut microbiota.

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jyh-Ming Liou, doctor; Phone Number: +886-972-651883; Email: nneder34@gmail.com

Study Locations

• Taiwan
  • Douliu, Taiwan, 64041
    • Recruiting
    • National Taiwan University Hospital Yunlin Branch
    • Principal Investigator: Yu-Jen Fang
    • Contact: Yu-Jen Fang, Doctor; Phone Number: +886-972-655374; Email: toby851072@yahoo.com.tw
  • Kaohsiung, Taiwan, 80756
    • Not yet recruiting
    • Kaohsiung Medical University Chung-Ho Memorial Hospital
    • Contact: JHENG-YI WU; Phone Number: +886-988-358359; Email: joywu@kmu.edu.tw
    • Principal Investigator: JHENG-YI WU
  • Taipei, Taiwan, 100225
    • Recruiting
    • National Taiwan University Hospital
    • Contact: Jyh-Ming Liou, doctor; Phone Number: +886-972-651883; Email: nneder34@gmail.com
    • Principal Investigator: Ming-Lun Han
  • Taipei, Taiwan, 10672
    • Recruiting
    • National Taiwan University Cancer Center
    • Contact: Jyh-Ming Liou, Doctor
    • Contact: Jyh-Ming Liou; Phone Number: +886-972-651883; Email: nneder34@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Patients older than 20 years-old underwent documented non-Bismuth containing 1st line H. pylori eradication with failure defined by positive 13C-Urea Breath Test (13C-UBT) at least 6 weeks after completion of therapy is eligible to the study.

Exclusion Criteria:

1. History of gastrectomy, surgery in the small intestine or colon
2. History of gastric malignancy, including adenocarcinoma or lymphoma
3. Allergic history, history of severe adverse effects or contraindication to antibiotics (Tetracycline, Metronidazole ), proton pump inhibitor, or probiotics
4. Pregnant or lactating women
5. Severe concurrent chronic or acute disease (e.g. renal failure, liver cirrhosis, or active malignancy)
6. Concomitant use of clopidogrel or warfarin
7. Recent (<4 weeks) use of antibiotics, or recent (<4 weeks) probiotic use duration >2 weeks
8. Not able to give consent on blinding or randomizatio
9. Not able to give consent by his or herself

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Probiotics packets; Probiotics contains 450 billion colony-forming units per packet. The compositions are maltose, lactic acid bacteria and bifidobacteria blend, cornstarch, silicon dioxide.	Dietary supplement: Probiotics packets; The treatment period is designed for 56 days: Bismuth containing quadruple therapy is performed from day 1~10 and Probiotics packets is taken from day 1~56.
Placebo Comparator: Placebo packets; The compositions are maltodextrin, silicon dioxide, sucralose	Dietary supplement: Placebo packets; The treatment period is designed for 56 days: Bismuth containing quadruple therapy is performed from day 1~10 and Placebo packets is taken from day 1~56.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the incidence of adverse effects after second line BQT between probiotic group (L) and placebo group (P) according to intentional to treat (ITT) and per-protocol (PP) analyses.	Adverse events are collected	From Day 0 to Day 10.
Evaluate the incidence of adverse effects after second line BQT between probiotic group (L) and placebo group (P) according to intentional to treat (ITT) and per-protocol (PP) analyses.	Adverse events are collected	From Day 0 to Day 56.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Eradication rate of second line BQT between two groups	13C-Urea breath tests are performed to check the eradication of Helicobacter pylori between two groups	From Day 0 to Day 56.
Dynamic changes in the gut microbiota between two groups	Stool sample collection for gut microbiota analysis	Day 0.
Dynamic changes in the metabolic pathway of gut microbiota between two groups	Stool sample collection for gut microbiota analysis	Day 0.
Re-infection rate 1 year and 3 years after second line eradication therapy	13C-Urea breath tests are performed to check the Helicobacter pylori infection	From Day 0 to Day 56.
Changes in the parameters of metabolic syndrome between two groups	Blood samples are collected for glucose, insulin, HbA1c, and lipid profiles, liver function tests, renal function tests as well as CRP. Also, transabdominal sonography for fatty liver severity assessment would be performed.	Day 0.
Eradication rate of second line BQT between two groups	13C-Urea breath tests are performed to check the eradication of Helicobacter pylori between two groups	From Day 0 to 1 year.
Eradication rate of second line BQT between two groups	13C-Urea breath tests are performed to check the eradication of Helicobacter pylori between two groups	From Day 0 to 3 years.
Dynamic changes in the gut microbiota between two groups	Stool sample collection for gut microbiota analysis	Day 10.
Dynamic changes in the gut microbiota between two groups	Stool sample collection for gut microbiota analysis	Day 56.
Dynamic changes in the gut microbiota between two groups	Stool sample collection for gut microbiota analysis	1 year.
Dynamic changes in the gut microbiota between two groups	Stool sample collection for gut microbiota analysis	3 years.
Dynamic changes in the metabolic pathway of gut microbiota between two groups	Stool sample collection for gut microbiota analysis	Day 10.
Dynamic changes in the metabolic pathway of gut microbiota between two groups	Stool sample collection for gut microbiota analysis	Day 56 .
Dynamic changes in the metabolic pathway of gut microbiota between two groups	Stool sample collection for gut microbiota analysis	1 year .
Dynamic changes in the metabolic pathway of gut microbiota between two groups	Stool sample collection for gut microbiota analysis	3 years.
Re-infection rate 1 year and 3 years after second line eradication therapy	13C-Urea breath tests are performed to check the Helicobacter pylori infection	From Day 0 to 1 year.
Re-infection rate 1 year and 3 years after second line eradication therapy	13C-Urea breath tests are performed to check the Helicobacter pylori infection	From Day 0 to 3 years.
Changes in the parameters of metabolic syndrome between two groups	Blood samples are collected for glucose, insulin, HbA1c, and lipid profiles, liver function tests, renal function tests as well as CRP. Also, transabdominal sonography for fatty liver severity assessment would be performed.	Day 56.
Changes in the parameters of metabolic syndrome between two groups	Blood samples are collected for glucose, insulin, HbA1c, and lipid profiles, liver function tests, renal function tests as well as CRP. Also, transabdominal sonography for fatty liver severity assessment would be performed.	1 year.
Changes in the parameters of metabolic syndrome between two groups	Blood samples are collected for glucose, insulin, HbA1c, and lipid profiles, liver function tests, renal function tests as well as CRP. Also, transabdominal sonography for fatty liver severity assessment would be performed.	3 years.

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Investigators: Principal Investigator: Ming-Lun Han, doctor, National Taiwan University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 29, 2021
• Primary Completion (Anticipated): April 29, 2023
• Study Completion (Anticipated): April 29, 2025

Study Registration Dates

• First Submitted: June 14, 2021
• First Submitted That Met QC Criteria: October 10, 2022
• First Posted (Actual): October 13, 2022

Study Record Updates

• Last Update Posted (Actual): October 21, 2022
• Last Update Submitted That Met QC Criteria: October 19, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: supplementary pylori; Bismuth quadruple therapy; H. pylori eradication
• Additional Relevant MeSH Terms: Gastrointestinal Diseases; Digestive System Diseases
• Other Study ID Numbers: 201912191MIPC

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