Tegoprazan-Based Therapies for H. Pylori Eradication: A Randomized Controlled Trial

Helicobacter pylori (H. pylori) infection remains a significant global health burden, strongly associated with peptic ulcer disease, gastric cancer, and mucosa-associated lymphoid tissue (MALT) lymphoma. Current international and Chinese guidelines endorse multidrug regimens as first-line eradication therapy. The predominant approach, particularly in China, is bismuth-containing quadruple therapy (BQT). This regimen combines a proton pump inhibitor (PPI) or a bismuth agent with two antibiotics (selected from agents such as clarithromycin, amoxicillin, quinolones, furazolidone, nitroimidazoles, or tetracycline), typically administered for 7 to 14 days.

Despite its established position, BQT faces substantial challenges in real-world implementation. Polypharmacy, inherent in administering four distinct medications, creates a significant burden for patients, increasing the risk of dosing errors and non-adherence. Furthermore, the combination of multiple antimicrobials and bismuth frequently leads to substantial adverse events (e.g., gastrointestinal disturbances, taste alterations), which further compromise treatment adherence. Suboptimal adherence is a well-recognized factor contributing to treatment failure and the alarming rise in antimicrobial resistance (AMR).

In response to these challenges, simplified dual therapies have emerged as a promising alternative strategy. These regimens pair a potent acid suppressant - either a traditional PPI or the newer, more potent potassium-competitive acid blocker (P-CAB) class - with high-dose amoxicillin. Accumulating evidence suggests that such optimized dual therapies can achieve eradication rates comparable to BQT in treatment-naïve populations. Crucially, they demonstrate superior tolerability and significantly improved adherence profiles due to reduced pill burden and fewer side effects. This combination leverages the critical role of profound acid suppression in enhancing amoxicillin's efficacy against H. pylori while minimizing the use of additional antibiotics, thereby potentially mitigating AMR development.

However, a significant knowledge gap exists within this evolving paradigm. While amoxicillin-based dual therapy has been studied, the comparative efficacy of tetracycline-based dual therapy remains unexamined in rigorous controlled clinical trials. Tetracycline, a key component of some BQT regimens and salvage therapies, possesses distinct antimicrobial properties against H. pylori. Understanding its performance within a simplified dual therapy framework, particularly under potent acid suppression, is essential for expanding therapeutic options.

Building upon promising preliminary investigations demonstrating that optimized PPI-amoxicillin dual therapy consistently achieves >90% eradication rates in treatment-naïve patients, this research aims to further advance the field. We propose a prospective, randomized controlled trial to directly compare the effectiveness of two novel dual therapy regimens for first-line H. pylori eradication. Both regimens will utilize tegoprazan, a next-generation P-CAB known for its rapid, potent, and sustained acid-inhibitory effects. Tegoprazan will be co-administered with either high-dose amoxicillin or tetracycline.