Second Line Bismuth Containing Quadruple Therapy With Supplementary Probiotic

H.Pylori Gastrointestinal Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05577572
• Other study ID #: 201912191MIPC
• Status: Recruiting
• Phase: N/A
• Start date: August 29, 2021
• Est. completion date: April 29, 2025

Study information

• Verified date: September 2022
• Source: National Taiwan University Hospital
• Contact: Jyh-Ming Liou, doctor
• Phone: +886-972-651883
• Email: nneder34[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: April 29, 2025
• Est. primary completion date: April 29, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Digestive System Diseases
• Gastrointestinal Diseases
• H.Pylori Gastrointestinal Disease

Intervention

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 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.

Locations

Country	Name	City	State
Taiwan	National Taiwan University Hospital Yunlin Branch	Douliu
Taiwan	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung
Taiwan	National Taiwan University Cancer Center	Taipei
Taiwan	National Taiwan University Hospital	Taipei

Sponsors (1)

Lead Sponsor	Collaborator
National Taiwan University Hospital

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	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	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.
Secondary	Dynamic changes in the gut microbiota between two groups	Stool sample collection for gut microbiota analysis	Day 0.
Secondary	Dynamic changes in the metabolic pathway of gut microbiota between two groups	Stool sample collection for gut microbiota analysis	Day 0.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	Dynamic changes in the gut microbiota between two groups	Stool sample collection for gut microbiota analysis	Day 10.
Secondary	Dynamic changes in the gut microbiota between two groups	Stool sample collection for gut microbiota analysis	Day 56.
Secondary	Dynamic changes in the gut microbiota between two groups	Stool sample collection for gut microbiota analysis	1 year.
Secondary	Dynamic changes in the gut microbiota between two groups	Stool sample collection for gut microbiota analysis	3 years.
Secondary	Dynamic changes in the metabolic pathway of gut microbiota between two groups	Stool sample collection for gut microbiota analysis	Day 10.
Secondary	Dynamic changes in the metabolic pathway of gut microbiota between two groups	Stool sample collection for gut microbiota analysis	Day 56 .
Secondary	Dynamic changes in the metabolic pathway of gut microbiota between two groups	Stool sample collection for gut microbiota analysis	1 year .
Secondary	Dynamic changes in the metabolic pathway of gut microbiota between two groups	Stool sample collection for gut microbiota analysis	3 years.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.