Journal Publication

Tegoprazan dual therapy misses non-inferiority mark against bismuth quadruple therapy for H. pylori

A 258-patient randomized trial found comparable eradication rates but failed to statistically confirm tegoprazan-amoxicillin dual therapy matches an optimized bismuth-based quadruple regimen.

A randomized trial of 258 treatment-naive Helicobacter pylori patients compared tegoprazan-amoxicillin dual therapy against an optimized bismuth-containing quadruple regimen and found the dual therapy did not meet its non-inferiority margin despite similar eradication rates.

By AppliedXLJuly 18, 2026

Executive Summary

A randomized trial testing whether a two-drug regimen could replace a four-drug bismuth-based regimen for Helicobacter pylori found similar eradication rates but did not statistically establish that the simpler regimen works as well.
Bismuth-containing quadruple therapy carries more pills, more side effects, and lower adherence in practice, so a validated two-drug alternative would simplify first-line treatment if it could match eradication performance.
A pooled analysis of prior trials mirrors the single-center result, showing the two-drug approach trails quadruple regimens that pair bismuth with amoxicillin and tetracycline or metronidazole.
The results argue against dropping bismuth quadruple therapy as first-line treatment and highlight that trial design, specifically which comparator regimen is used, can make a simpler regimen look artificially competitive.

The stake

Helicobacter pylori infection is typically treated with multidrug regimens, and bismuth-containing quadruple therapy, which combines a proton pump inhibitor, bismuth, and two antibiotics, is a standard first-line option when eradication rates for it are optimized. A two-drug regimen combining tegoprazan, a potassium-competitive acid blocker, with amoxicillin alone would simplify treatment and reduce antibiotic exposure if it could match quadruple therapy's eradication performance. Because bismuth quadruple therapy's own eradication efficacy varies across settings, the researchers argued that comparator choice determines whether a simpler regimen appears competitive in a trial. Comparator

How it was done

The trial was a non-inferiority randomized controlled trial conducted at Qilu Hospital of Shandong University between March 2023 and January 2024. It randomized 258 treatment-naive H. pylori-infected patients to 14 days of tegoprazan-amoxicillin dual therapy or esomeprazole-amoxicillin-tetracycline bismuth quadruple therapy. The primary outcome was eradication rate, assessed separately in intention-to-treat, modified intention-to-treat, and per-protocol populations. Secondary outcomes were adverse events and treatment compliance. The trial was paired with a meta-analysis of prior randomized trials comparing the same dual-therapy approach against bismuth quadruple regimens. Comparator

The result

Eradication rates ran 82.95% versus 90.70% in the intention-to-treat analysis (P=0.066), 84.25% versus 91.41% in the modified intention-to-treat analysis (P=0.080), and 89.17% versus 95.80% in the per-protocol analysis (P=0.052), for dual therapy versus the bismuth quadruple regimen. None of the three comparisons reached statistical significance, and the trial's stated non-inferiority margin was not met by dual therapy despite the numerically similar rates. Adverse events occurred in 20.16% of dual-therapy patients versus 26.36% on quadruple therapy (P=0.238), and compliance was 96.12% versus 95.35% (P=0.758): neither difference was statistically significant. Comparator

The meta-analysis

The companion meta-analysis pooled seven trial groups comparing tegoprazan-amoxicillin dual therapy against bismuth-containing quadruple regimens. In a subgroup analysis by antibiotic combination, dual therapy showed a lower intention-to-treat eradication rate than bismuth quadruple regimens built on amoxicillin plus tetracycline or metronidazole, a risk ratio of 0.90 (95% CI: 0.84-0.97, P=0.006). That finding, drawn across multiple trials rather than one center, reinforces the single-site result and extends it: the comparator's specific antibiotic pairing, not just its class, shapes how the two-drug regimen performs by comparison. Comparator

What it changes for practice

The authors concluded that comparator selection is critical when designing eradication trials, since bismuth quadruple therapy's own performance varies with which antibiotics it pairs with bismuth. For practice, the results do not support substituting tegoprazan-amoxicillin dual therapy for an optimized bismuth quadruple regimen as first-line treatment, even though the simpler regimen showed similar rates of adverse events and comparable compliance. Comparator

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