Bacillus Probiotics With Bismuth Quadruple Therapy for Helicobacter Pylori Infection

NCT07827170 | Not Yet Recruiting DMC

• 1 other identifier: IRB.TAHN 178
• Study Type: interventional
• Target: 336
• Locations: 1 country
• Sites: 1

Brief Summary

Helicobacter pylori (H. pylori) is a very common gastrointestinal disease that colonises the human gastric mucosa and is a primary risk factor for chronic gastritis, peptic ulcer disease, and gastric cancer. The standard first-line treatment for H. pylori eradication is bismuth-containing quadruple therapy. While effective, this aggressive, multi-antibiotic regimen frequently induces significant gastrointestinal adverse effects and severe disruption of the normal gut microbiota (dysbiosis). These side effects often lead to poor patient compliance, which in turn contributes to treatment failure and the increasing global challenge of antibiotic resistance. Emerging clinical evidence strongly supports the use of probiotics as an adjuvant therapy to alleviate antibiotic-associated side effects and significantly aid in restoring intestinal balance. Spore-forming Bacillus species, specifically Bacillus clausii, Bacillus subtilis, and Bacillus coagulans, are particularly advantageous due to their natural resistance to acidic gastric conditions and concurrent antibiotic administration, allowing them to remain viable and active during the intensive eradication therapy. This clinical trial is designed as a randomised, double-blind, placebo-controlled study to evaluate the clinical efficacy, adverse effects, and treatment adherence of a standard four-drug bismuth-containing regimen for the treatment of H. pylori infection when combined with single-strain and multi-strain Bacillus probiotics. The trial is conducted in the Gastroenterology Department of Tam Anh Hospital. 336 participants diagnosed with H. pylori infection and prescribed the standard 14-day bismuth-containing quadruple therapy are randomly divided and allocated to receive either a single-strain probiotic (LiveSpo Clausy), a multi-strain probiotic (LiveSpo DIA 30), or an identical placebo. Over 8 weeks of follow-up, participants will be assessed at predefined time points for antibiotic-associated adverse events, gastrointestinal symptoms, stool form, treatment adherence, and Helicobacter pylori eradication status. Stool samples will be collected before and after treatment to evaluate faecal IgA levels, the presence of Bacillus strains, and changes in gut microbiota using real-time PCR, ELISA, and 16S rRNA sequencing.

Conditions

Gastrointestinal Dysbiosis; Helicobacter Pylori Infection; Antibiotic-associated Adverse Events

Keywords

Bacillus spore; Gut Dysbiosis; Helicobacter pylori; Gut microbiome; Bismuth quadruple therapy

Outcome Measures

Primary Outcomes (3)

• Antibiotic-Associated Adverse Event Rate and Severity

  The proportion and severity of antibiotic-associated adverse events during H. pylori eradication therapy are assessed using the Antibiotic-Associated Adverse Events Questionnaire (AAE-Q) during the first 2 weeks of treatment. The assessed symptoms include: fatigue, loss of appetite, dizziness, headache, diarrhoea, and nausea/vomiting. The key evaluation time point will be week 2, with changes assessed from baseline/week 0 to week 2. The week 1, 4, and 8 visits will serve as interim supportive time points.

  Weeks 0, 1, 2, 4 and 8

• Change in Gastrointestinal Symptom Score

  Gastrointestinal symptoms are assessed using the Gastrointestinal Symptom Rating Scale (GSRS), at baseline, after completion of H. pylori eradication therapy, and during the post-treatment follow-up period. The key evaluation time point will be week 2, with changes assessed from baseline/week 0 to week 2. The week 8 visits will serve as interim supportive time points.

  Weeks 0, 2, and 8

• Change in Stool Consistency

  Stool consistency will be assessed using the Bristol Stool Scale (BSS) at baseline, after completion of H. pylori eradication therapy, and during the post-treatment follow-up period. The key evaluation time point will be week 2, with changes assessed from baseline/week 0 to week 2. The week 8 visits will serve as interim supportive time points.

  Weeks 0, 2, and 8

Secondary Outcomes (2)

• Treatment Adherence

  Weeks 1 and 2

• Pill Count Adherence Rate

  Weeks 1 and 2

Other Outcomes (4)

• H. pylori Eradication Rate

  Weeks 0 and 8

• Change in Fecal Secretory IgA Concentration

  Weeks 0, 2 and 8

• Gut microbiota composition

  Weeks 0 and 2

Study Arms (3)

Control group

PLACEBO COMPARATOR

The Control group receives the standard treatment regimen, combined with RO water at a dose of 3 ampoules/day for 2 weeks; then continues using 2 ampoules/day for the next 6 weeks. The probiotic product is used at least 2 hours apart from the antibiotic dose. The BQT routine treatment regimen is: * Esomeprazole 40 mg: take 1 tablet twice daily, 30-60 minutes before meals. * Tetracycline 500 mg: take 1 tablet four times daily, 30 minutes after meals. * Tinidazole 500 mg: take 1 tablets three times daily (after breakfast, lunch, dinner) 30 minutes after meals. * Bismuth subcitrate 120 mg: take 1 tablet four times daily, 30 minutes after meals.

Other: RO water

Clausy group

EXPERIMENTAL

The Clausy group receives the standard treatment regimen, combined with RO water plus B. clausii at 2 billion CFU/5 ml (LiveSpo® CLAUSY) at a dose of 3 ampoules/day for 2 weeks; then continues using 2 ampoules/day for the next 6 weeks. The probiotic product is used at least 2 hours apart from the antibiotic dose. The BQT routine treatment regimen is: * Esomeprazole 40 mg: take 1 tablet twice daily, 30-60 minutes before meals. * Tetracycline 500 mg: take 1 tablet four times daily, 30 minutes after meals. * Tinidazole 500 mg: take 1 tablets three times daily (after breakfast, lunch, dinner) 30 minutes after meals. * Bismuth subcitrate 120 mg: take 1 tablet four times daily, 30 minutes after meals.

Combination Product: LiveSpo CLAUSY

Dia 30 group

EXPERIMENTAL

The Dia 30 group receives the standard treatment regimen, combined with RO water plus B. Clausii, B. subtilis, B. coagulans at 5 billion CFU/5 ml (LiveSpo® DIA 30) at a dose of 3 ampoules/day for 2 weeks; then continues using 2 ampoules/day for the next 6 weeks. The probiotic product is used at least 2 hours apart from the antibiotic dose. The BQT routine treatment regimen is: * Esomeprazole 40 mg: take 1 tablet twice daily, 30-60 minutes before meals. * Tetracycline 500 mg: take 1 tablet four times daily, 30 minutes after meals. * Tinidazole 500 mg: take 1 tablets three times daily (after breakfast, lunch, dinner) 30 minutes after meals. * Bismuth subcitrate 120 mg: take 1 tablet four times daily, 30 minutes after meals.

Combination Product: LiveSpo DIA30

Interventions

RO water OTHER

RO water (Aquafina, PepsiCo) produced under ISO 9001:2015 and ISO 22000:2018 standards. The RO water ampoules are produced using a similar process as the LiveSpo Clausy / Dia30 but contain 5 mL of high-quality RO water from Aquafina.

Control group

LiveSpo CLAUSY COMBINATION_PRODUCT

LiveSpo® CLAUSY has a registration number 4071/2021/ĐKSP issued by the Food Safety Department of the Ministry of Health in Vietnam.

Clausy group

LiveSpo DIA30 COMBINATION_PRODUCT

LiveSpo® DIA30 has a registration number 6547/2019/ĐKSP issued by the Food Safety Department of the Ministry of Health in Vietnam.

Dia 30 group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients aged 18 to 65 years;
• Diagnosed with H. pylori infection by the 13C-urea breath test or the rapid urease test;
• Indicated for H. pylori eradication treatment with the four-drug bismuth regimen (BQT);
• Agree to participate in the study and have been informed and signed the consent form

You may not qualify if:

• Active bleeding gastric or duodenal ulcer.
• Use of antibiotics, acid-suppressing drugs (PPIs, H2RAs), non-steroidal anti-inflammatory drugs (NSAIDs), laxatives, antidiarrheals, or probiotics (excluding yogurt) within at least 4 weeks before participating in the study, except for laxatives used as part of the study's endoscopic preparation procedure.
• Chronic inflammatory bowel disease (IBD), acute intestinal infection, gastrointestinal cancer (stomach cancer, colon cancer), acute or chronic pancreatitis, immunosuppression (including prolonged corticosteroid use), or psychiatric disorders.
• Alcohol abuse, history of delirium tremens, or alcoholic liver disease.
• Pregnant or breastfeeding women.

Sponsors & Collaborators

• Anabio R&D: lead
• Tam Anh Research Institute: collaborator

Study Sites (1)

Tam Anh Ha Noi General Hospital

Hanoi, Vietnam

Location

Related Publications (16)

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Study Officials

• Tien Tran Dao, MSc, M.D.

  Ha Noi Medical University

  PRINCIPAL INVESTIGATOR

• Khanh Tran Van, Prof.M.D

  Ha Noi Medical University

  STUDY CHAIR

• Anh Nguyen Thi Van

  Spobio Research Center, Anabio R&D

  STUDY CHAIR

Central Study Contacts

Tien Tran Dao

CONTACT

(+84) 945121519.; daotrantien1982@gmail.com

Phuong Ho Thi Ha

CONTACT

(+84) 0364179126; hothihaphuong@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 14, 2026
• First Posted: September 18, 2026
• Study Start: October 1, 2026
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: September 22, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, CSR
• Time Frame: Data requests can be submitted 9 months after article publication and will be made accessible for up to 24 months. Extensions will be considered on a case-by-case basis.
• Access Criteria: Access to trial IPD can be requested by qualified researchers engaging in independent scientific research. It will be provided following the review and approval of a study protocol, informed consent form (ICF), and clinical study report (CSR). For more information or to sub

Locations

VN (1)