Tegoprazan-Based Dual Therapy With Amoxicillin vs Tetracycline for H. Pylori Eradication

Not Applicable

Recruiting

• Conditions: Helicobacter Pylori Eradication; High-dose Dual Therapy
• Interventions: Drug: Tegoprazan; Drug: Amoxicillin 250Mg Cap; Drug: Tetracycline 500 Mg; Drug: Bismuth

• Registration Number: NCT06977841
• Lead Sponsor: Zhongshan Hospital (Xiamen), Fudan University

Brief Summary

Current first-line Helicobacter pylori eradication protocols involve multidrug regimens comprising a proton pump inhibitor (PPI) or bismuth agent combined with dual antibiotics (e.g., clarithromycin, amoxicillin, quinolones, furazolidone, nitroimidazoles, or tetracycline) administered for 7-14 days. In China, the bismuth-containing quadruple therapy (BQT) remains the standard first-line treatment for H. pylori infection. However, BQT implementation is challenged by polypharmacy burdens, substantial adverse events, and suboptimal treatment adherence. Emerging evidence suggests that simplified dual therapies pairing acid suppressants (PPIs or potassium-competitive acid blockers \[P-CABs\]) with high-dose amoxicillin achieve comparable eradication rates to BQT while demonstrating superior tolerability and adherence profiles. Notably, the comparative efficacy of tetracycline-based versus amoxicillin-based dual regimens remains unexamined in controlled clinical trials. Our preliminary investigations established that optimized PPI-amoxicillin dual therapy achieves \>90% eradication rates in treatment-naïve populations. Building on these findings, this prospective randomized controlled trial will comparatively assess the effectiveness of tegoprazan-a novel P-CAB exhibiting potent acid inhibition-when co-administered with either amoxicillin or tetracycline in H. pylori-positive adults. The investigation aims to establish an evidence framework for streamlining eradication protocols through pharmacodynamic optimization while mitigating antimicrobial resistance development.

Detailed Description

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.

Study Timeline

• Study First Submitted: 2025-05-10
• Study First Submitted QC: 2025-05-10
• Study First Posted: 2025-05-18
• Study Start: 2025-06-10
• Status Verified: 2025-08
• Last Update Submitted: 2025-08-14
• Last Update Posted: 2025-08-20
• Primary Completion: 2026-03-30
• Study Completion: 2026-05-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 87

Inclusion Criteria

1. Age from 18 to 65 years;
2. H.pylori infection diagnosed by 13C-urea breath test;
3. The patient infected with Helicobacter pylori has never undergone eradication therapy.

Exclusion Criteria

1. Allergy to any of the medications;
2. Zollinger-Ellison syndrome, GC, Upper gastrointestinal bleeding, or Active peptic ulcer;
3. Coexistence of significant concomitant illnesses, including heart disease, renal failure, hepatic disease, previous abdominal surgery, lactation, or pregnancy;
4. Patients who had used PPI/P-CAB drugs, and antibiotics in the past 12 weeks;
5. Unwillingness to participate in this study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Tegoprazan-Amoxicillin Dual Therapy	Tegoprazan	Tegoprazan 50 mg orally twice daily (BID) before meals; Amoxicillin 750 mg orally four times daily (QID) after meals; Both administered for 14 consecutive days.
Tegoprazan-Amoxicillin Dual Therapy	Amoxicillin 250Mg Cap	Tegoprazan 50 mg orally twice daily (BID) before meals; Amoxicillin 750 mg orally four times daily (QID) after meals; Both administered for 14 consecutive days.
Tegoprazan-Tetracycline Dual Therapy	Tegoprazan	Tegoprazan 50 mg orally twice daily (BID) before meals; Tetracycline 500 mg orally four times daily (QID) after meals; Both administered for 14 consecutive days.
Tegoprazan-Amoxicillin-Tetracycline Triple Therapy	Tegoprazan	Tegoprazan 50 mg orally twice daily (BID) before meals; Amoxicillin 1 g orally twice daily (BID) after meals; Tetracycline 500 mg orally three times daily (TID) after meals; All administered for 14 consecutive days.
Tegoprazan-Amoxicillin-Tetracycline Triple Therapy	Amoxicillin 250Mg Cap	Tegoprazan 50 mg orally twice daily (BID) before meals; Amoxicillin 1 g orally twice daily (BID) after meals; Tetracycline 500 mg orally three times daily (TID) after meals; All administered for 14 consecutive days.
Tegoprazan-Amoxicillin-Tetracycline Triple Therapy	Tetracycline 500 Mg	Tegoprazan 50 mg orally twice daily (BID) before meals; Amoxicillin 1 g orally twice daily (BID) after meals; Tetracycline 500 mg orally three times daily (TID) after meals; All administered for 14 consecutive days.
Tegoprazan-Tetracycline Dual Therapy	Tetracycline 500 Mg	Tegoprazan 50 mg orally twice daily (BID) before meals; Tetracycline 500 mg orally four times daily (QID) after meals; Both administered for 14 consecutive days.
Tegoprazan-Amoxicillin-Tetracycline-Bismuth Quadruple Therapy	Tegoprazan	Tegoprazan 50 mg orally twice daily (BID) before meals; Amoxicillin 1 g orally twice daily (BID) after meals; Tetracycline 500 mg orally three times daily (TID) after meals; Bismuth agent (bismuth potassium citrate) 220 mg orally twice daily (BID) after meals; All administered for 14 consecutive days.
Tegoprazan-Amoxicillin-Tetracycline-Bismuth Quadruple Therapy	Amoxicillin 250Mg Cap	Tegoprazan 50 mg orally twice daily (BID) before meals; Amoxicillin 1 g orally twice daily (BID) after meals; Tetracycline 500 mg orally three times daily (TID) after meals; Bismuth agent (bismuth potassium citrate) 220 mg orally twice daily (BID) after meals; All administered for 14 consecutive days.
Tegoprazan-Amoxicillin-Tetracycline-Bismuth Quadruple Therapy	Tetracycline 500 Mg	Tegoprazan 50 mg orally twice daily (BID) before meals; Amoxicillin 1 g orally twice daily (BID) after meals; Tetracycline 500 mg orally three times daily (TID) after meals; Bismuth agent (bismuth potassium citrate) 220 mg orally twice daily (BID) after meals; All administered for 14 consecutive days.
Tegoprazan-Amoxicillin-Tetracycline-Bismuth Quadruple Therapy	Bismuth	Tegoprazan 50 mg orally twice daily (BID) before meals; Amoxicillin 1 g orally twice daily (BID) after meals; Tetracycline 500 mg orally three times daily (TID) after meals; Bismuth agent (bismuth potassium citrate) 220 mg orally twice daily (BID) after meals; All administered for 14 consecutive days.
Tegoprazan-Amoxicillin Dual Therapy	Tegoprazan	-
Tegoprazan-Amoxicillin Dual Therapy	Amoxicillin 250Mg Cap	-
Tegoprazan-Tetracycline Dual Therapy	Tegoprazan	-
Tegoprazan-Tetracycline Dual Therapy	Tetracycline 500 Mg	-
Tegoprazan-Amoxicillin-Tetracycline Triple Therapy	Tegoprazan	-
Tegoprazan-Amoxicillin-Tetracycline Triple Therapy	Amoxicillin 250Mg Cap	-
Tegoprazan-Amoxicillin-Tetracycline Triple Therapy	Tetracycline 500 Mg	-
Tegoprazan-Amoxicillin-Tetracycline-Bismuth Quadruple Therapy	Tegoprazan	-
Tegoprazan-Amoxicillin-Tetracycline-Bismuth Quadruple Therapy	Amoxicillin 250Mg Cap	-
Tegoprazan-Amoxicillin-Tetracycline-Bismuth Quadruple Therapy	Tetracycline 500 Mg	-
Tegoprazan-Amoxicillin-Tetracycline-Bismuth Quadruple Therapy	Bismuth	-

Primary Outcome Measures

Name	Time	Method
H. pylori eradication rate	44 days	Assessed by 13C-urea breath test (13C-UBT) at 30 days post-treatment. Eradication success was defined as a negative result (delta over baseline value \<4‰).

Secondary Outcome Measures

Name	Time	Method
Frequency of the adverse events	44 days	Incidence rate of the adverse events, including dyspepsia, nausea, vomiting, abdominal pain, bloating, diarrhea, dizziness, headache, skin rash, fatigue and fever.
Compliance rate of the drugs	44 days	Compliance is defined as good when they had taken more than 80% of the total medication.

Trial Locations

Locations (2)

Zhongshan Hospital (Xiamen), Fudan University; 🇨🇳 Xiamen, Fujian, China

Zhongshan Hospital (Xiamen), Fudan University; 🇨🇳 Xiamen, Fujian, China