Metronidazole‑based drug combination versus standard therapy for Helicobacter pylori infection in adults

The primary objective is to demonstrate the non‑inferiority of the fixed‑dose combination of metronidazole, bismuth oxide and tetracycline hydrochloride compared with the standard concomitant non‑bismuth quadruple regimen for first‑line eradication of Helicobacter pylori infection, thereby establishing an alternative therapeutic option with comparable efficacy. Secondary objectives include:

• Evaluation of the eradication rate in the per‑protocol population to confirm the robustness of the primary analysis.
• Assessment of superiority in eradication rates, conditional on achievement of non‑inferiority.
• Comparison of patient compliance between treatment arms.
• Comparison of safety and tolerability by measuring the frequency of adverse events.

The trial enrolled adult participants of both sexes with a diagnosed active Helicobacter pylori infection confirmed by gastroscopy and CLO testing. Inclusion required age ≥ 18 years, no prior eradication therapy, a clear indication for treatment, ability to follow the prescribed dosing schedule, and provision of written informed consent. The study population consisted of patients meeting these criteria; no specific dietary, physical activity, or habit restrictions were described. The sponsor did not provide information on the total number of enrolled subjects.

The study is a randomized, single‑blind, parallel‑group Phase III non‑inferiority trial evaluating a fixed‑dose combination of metronidazole, bismuth oxide and tetracycline hydrochloride against a standard concomitant non‑bismuth quadruple regimen for first‑line eradication of Helicobacter pylori infection in adults aged ≥ 18 years with active infection confirmed by gastroscopy and CLO test and no prior eradication therapy. After an initial screening visit to verify eligibility, participants are randomized to one of two treatment arms and receive the assigned oral regimen for the prescribed treatment period. Follow‑up visits include a post‑treatment assessment to obtain a urea breath test for determination of eradication status, safety evaluation, and collection of adherence data; the final end‑of‑study visit completes the safety follow‑up. Primary efficacy is assessed by the proportion of participants with a negative urea breath test in the microbiological intention‑to‑treat set, while secondary analyses comprise per‑protocol eradication rates, superiority testing, adherence ≥90 % based on pill counts and diaries, incidence of adverse events, and discontinuations due to adverse events. Participant involvement spans approximately six to eight weeks from randomization through the end‑of‑study assessment. Early termination may occur for medically significant adverse events, failure to adhere to ≥90 % of the prescribed medication, withdrawal of informed consent, or major protocol violations. The recruitment period is planned from June 2026 to June 2027, resulting in an overall study duration of roughly twelve months.

The investigational product is a fixed‑dose combination tablet (Verisfield f.c.) that contains tetracycline hydrochloride, metronidazole and bismuth oxide. It is a film‑coated tablet intended for oral administration and is supplied at a dose of “4 Other” as defined by the study protocol.

The comparator arm includes a film‑coated tablet of clarithromycin supplied as 500 mg tablets for oral use, with a dose of 1 g per administration.

Amoxicillin is provided as dispersible tablets containing 1 g of active substance; the dose specified for the study is 2 g per administration, taken orally.

Esomeprazole is administered as a gastro‑resistant hard capsule, 80 mg per capsule, for oral use. This proton‑pump inhibitor is used as an auxiliary medication in the regimen.

Metronidazole is supplied as hard capsules containing 500 mg of active ingredient; the dose listed for the study is 1 g per administration, taken orally.

A diagnostic agent, 13C‑urea powder for oral solution, is used for Helicobacter pylori testing. The preparation is administered orally in a single dose of 75 mg.

Efficacy will be evaluated primarily by the proportion of participants achieving successful clearance of Helicobacter pylori infection, defined as a negative Urea Breath Test performed after completion of the eradication regimen. The primary analysis will compare eradication rates between the fixed‑dose combination arm and the standard concomitant therapy arm in the microbiological intention‑to‑treat (mITT) population.

Secondary efficacy assessments include:

• Eradication rate in the Per‑Protocol (PP) population.
• Statistical comparison of eradication rates (mITT and PP) to test for superiority of the fixed‑dose combination over the active comparator.
• Compliance, measured as the proportion of participants who ingest ≥90 % of prescribed doses, based on pill counts and patient diary entries.
• Incidence of adverse events, expressed as the proportion of participants reporting at least one event.
• Tolerability, defined as the proportion of participants who discontinue treatment prematurely due to adverse events.

All microbiological assessments will be conducted using the validated Urea Breath Test at a post‑treatment visit scheduled after the full course of therapy. Compliance data will be collected at each study visit through unit counts and review of patient diaries. Adverse events and tolerability will be recorded continuously throughout the treatment period and at the final follow‑up visit. Statistical analyses will employ non‑inferiority margins for the primary endpoint and appropriate superiority testing for secondary comparisons, using predefined analysis sets (mITT and PP).