Pylori Duo for Adjunctive Treatment and Prevention of Recurrence of Helicobacter Pylori Infection

This is a randomized, double-blind, placebo-controlled, single-center interventional clinical trial designed to evaluate the efficacy and safety of Pylori Duo as an adjunctive treatment in adult patients with confirmed Helicobacter pylori infection. Approximately 140 patients aged 18 to 70 years with a positive 13C-urea breath test and gastric biopsy performed before study initiation will be enrolled.

Participants will be randomly assigned to one of two parallel treatment groups. Group A will receive standard quadruple therapy consisting of omeprazole plus Pylera® in combination with placebo for 10 days, followed by placebo for 3 months. Group B will receive the same standard quadruple therapy in combination with Pylori Duo for 10 days, followed by Pylori Duo for 3 months. Both investigators and participants will remain blinded to treatment allocation throughout the study.

The primary objective of the study is to evaluate the effect of Pylori Duo on the management of gastrointestinal adverse effects associated with standard eradication therapy. Secondary objectives include evaluation of H. pylori eradication rate, recurrence of infection at 3 and 12 months after treatment, gastrointestinal symptoms assessed using the Gastrointestinal Symptom Rating Scale (GSRS), gastrointestinal quality of life assessed using the Nepean Dyspepsia Index-Short Form (NDI-SF), and safety and tolerability. Safety assessments will include the recording of adverse events, evaluation of their potential relationship to the study product, and treatment adherence monitoring.

Participants will attend scheduled follow-up visits during treatment and post-treatment follow-up. A 13C-urea breath test will be performed 6 to 8 weeks after completion of Phase I treatment to assess eradication. Follow-up will continue for 3 months after treatment completion, and a telephone assessment will be conducted at 12 months to evaluate recurrence. Statistical analyses will be performed using both intention-to-treat and per-protocol populations.

• Omeprazole (Drug): Omeprazole will be administered as part of the standard quadruple eradication therapy for Helicobacter pylori infection during the 10-day treatment phase.
• Pylera (Bismuth subcitrate potassium, metronidazole, tetracycline) given in combination with omeprazole (Drug): Pylera® will be administered in combination with omeprazole as part of the standard quadruple eradication therapy for Helicobacter pylori infection during the 10-day treatment phase.
• Pylori Duo (Dietary supplement): Pylori Duo is a dietary supplement containing Lactobacillus rhamnosus and dried licorice extract. Participants assigned to the experimental arm will receive Pylori Duo in combination with standard quadruple therapy for 10 days, followed by Pylori Duo for 3 months during the post-treatment phase.
• Placebo (Other): Placebo capsules identical in appearance to Pylori Duo, but without pharmacologically active ingredients, will be administered in combination with standard quadruple therapy for 10 days, followed by placebo for 3 months during the post-treatment phase.

Primary outcomes

• Gastrointestinal adverse effects associated with standard eradication therapy [Up to 3 months after treatment initiation]: Assessment of the effect of Pylori Duo on the management of gastrointestinal adverse effects associated with standard Helicobacter pylori eradication therapy. Gastrointestinal tolerability will be evaluated during the treatment period and follow-up.

Secondary outcomes

• Helicobacter pylori eradication rate [6 to 8 weeks after completion of the 10-day treatment phase]: Eradication of H. pylori will be assessed by negative 13C-urea breath test performed 6 to 8 weeks after completion of Phase I treatment. Gastric biopsy may also be considered according to protocol-defined diagnostic assessment.
• Recurrence of Helicobacter pylori infection [3 months and 12 months after completion of treatment]: Recurrence of H. pylori infection will be evaluated during follow-up at 3 and 12 months after treatment based on post-treatment clinical assessment and protocol-defined follow-up procedures.
• Change from baseline in Gastrointestinal Symptom Rating Scale overall score [Baseline and 3 months after treatment initiation]: Gastrointestinal symptoms will be assessed using the 15-item Gastrointestinal Symptom Rating Scale. Each item is scored from 1, indicating no troublesome symptoms, to 7, indicating very troublesome symptoms. The overall score is calculated as the mean of the 15 item scores and ranges from 1 to 7. Higher scores indicate greater gastrointestinal symptom severity and therefore a worse outcome. Change from baseline will be evaluated during the follow-up period.
• Change from baseline in Short Form Nepean Dyspepsia Index total score [Baseline and 3 months after treatment initiation]: Gastrointestinal health-related quality of life will be assessed using the 10-item Short Form Nepean Dyspepsia Index. The total score ranges from 0 to 100. Higher scores indicate better gastrointestinal health-related quality of life and therefore a better outcome. Change from baseline will be evaluated during the follow-up period.
• Participants with adverse events [Up to 3 months after the first dose]: Number and percentage of participants who experience at least one adverse event during the assessment period.
• Participants with study product-related adverse events [Up to 3 months after the first dose]: Number and percentage of participants who experience at least one adverse event considered by the investigator to be related to the study product.
• Treatment adherence [Up to 3 months after the first dose]: Treatment adherence will be reported as the percentage of prescribed study product doses taken. The percentage will be calculated as the number of doses taken divided by the number of doses prescribed, multiplied by 100. Higher percentages indicate greater treatment adherence.

Sex: All, ages: 18 Years to 70 Years

Inclusion Criteria:

* Adults aged 18 to 70 years.
* Confirmed Helicobacter pylori infection prior to treatment, as determined by a positive 13C-urea breath test (13C-UBT) and gastric biopsy.
* No previous H. pylori eradication therapy.
* Ability and willingness to provide written informed consent.

Exclusion Criteria:

* Significant underlying conditions that, in the opinion of the treating physician, would preclude participation in the study, including hepatic insufficiency (aspartate aminotransferase or alanine aminotransferase >3 times the upper limit of normal), renal insufficiency (creatinine ≥2.0 mg/dL or glomerular filtration rate <50 mL/min), immunosuppression, malignant tumors, coronary heart disease or coronary artery stenosis ≥75%, thyroid disease, pulmonary disease, or any other serious medical condition.
* Pregnancy, breastfeeding, or unwillingness to use contraception during the study.
* Active gastrointestinal bleeding.
* History of upper gastrointestinal tract surgery.
* History of allergic reactions to medications included in the treatment regimen.
* Use of bismuth-containing agents, antibiotics, proton pump inhibitors, or other relevant medications within 4 weeks prior to treatment.
* Behaviors that may increase the risk of illness, including excessive alcohol consumption or substance abuse.
* Negative repeat urea breath test prior to treatment initiation.
* Unwillingness or inability to provide informed consent.

• Sergio Chamorro Benítez, Medicine, Principal investigator, Hospital Parque Vegas Altas, Don Benito (Badajoz)