Clinical trial NCT05577572: Second Line Bismuth Containing Quadruple Therapy With Supplementary Probiotic
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: H.Pylori Gastrointestinal Disease
Keywords: supplementary pylori
Bismuth quadruple therapy
H. pylori eradication
Lead sponsor: National Taiwan University Hospital
Sponsor class: OTHER
First posted: 2022-10-13
Enrollment: 200
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: SUPPORTIVE_CARE

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

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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.
timeFrame: From Day 0 to Day 10.
measure: 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.
timeFrame: From Day 0 to Day 56.
Secondary outcomes:
measure: Eradication rate of second line BQT between two groups
timeFrame: From Day 0 to Day 56.
measure: Dynamic changes in the gut microbiota between two groups
timeFrame: Day 0.
measure: Dynamic changes in the metabolic pathway of gut microbiota between two groups
timeFrame: Day 0.
measure: Re-infection rate 1 year and 3 years after second line eradication therapy
timeFrame: From Day 0 to Day 56.
measure: Changes in the parameters of metabolic syndrome between two groups
timeFrame: Day 0.
measure: Eradication rate of second line BQT between two groups
timeFrame: From Day 0 to 1 year.
measure: Eradication rate of second line BQT between two groups
timeFrame: From Day 0 to 3 years.
measure: Dynamic changes in the gut microbiota between two groups
timeFrame: Day 10.
measure: Dynamic changes in the gut microbiota between two groups
timeFrame: Day 56.
measure: Dynamic changes in the gut microbiota between two groups
timeFrame: 1 year.
measure: Dynamic changes in the gut microbiota between two groups
timeFrame: 3 years.
measure: Dynamic changes in the metabolic pathway of gut microbiota between two groups
timeFrame: Day 10.
measure: Dynamic changes in the metabolic pathway of gut microbiota between two groups
timeFrame: Day 56 .
measure: Dynamic changes in the metabolic pathway of gut microbiota between two groups
timeFrame: 1 year .
measure: Dynamic changes in the metabolic pathway of gut microbiota between two groups
timeFrame: 3 years.
measure: Re-infection rate 1 year and 3 years after second line eradication therapy
timeFrame: From Day 0 to 1 year.
measure: Re-infection rate 1 year and 3 years after second line eradication therapy
timeFrame: From Day 0 to 3 years.
measure: Changes in the parameters of metabolic syndrome between two groups
timeFrame: Day 56.
measure: Changes in the parameters of metabolic syndrome between two groups
timeFrame: 1 year.
measure: Changes in the parameters of metabolic syndrome between two groups
timeFrame: 3 years.
Other outcomes:
Locations:
city: Douliu
country: Taiwan
facility: National Taiwan University Hospital Yunlin Branch
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Chung-Ho Memorial Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Cancer Center
Study officials:
affiliation: National Taiwan University Hospital
name: Ming-Lun Han, doctor
role: PRINCIPAL_INVESTIGATOR
References: