Vonoprazan-Tetracycline Dual Regimen as Rescue Therapy for Helicobacter pylori Infection: Randomized Controlled Trial
Vonoprazan plus tetracycline cleared Helicobacter pylori as well as standard bismuth four-drug rescue therapy, with far fewer side effects and better completion.
*Open-label randomized noninferiority trial; Level 1b (OCEBM).
*Open-label randomized noninferiority trial; Level 1b (OCEBM).
Citation
Gao W, Li J, Yang G, et al. Vonoprazan-Tetracycline Dual Regimen as Rescue Therapy for Helicobacter pylori Infection: Randomized Controlled Trial. Gastroenterology. 2026;170:1473–1483. doi:10.1053/j.gastro.2026.01.008.
Background
After a failed attempt to eliminate Helicobacter pylori, rescue treatments often require multiple drugs and can be hard to tolerate. This trial tested whether a simpler two-drug option works as well as standard rescue therapy.
Patients
Adults aged 18–80 years with Helicobacter pylori confirmed by carbon-13 urea breath test and at least 1 prior eradication failure. Exclusions included recent acid-suppressing drugs, antibiotics, or bismuth (within 4 weeks), pregnancy or breastfeeding, severe major illness, or allergy to study drugs.
Intervention
Vonoprazan 20 mg twice daily plus tetracycline 500 mg three times daily for 14 days.
Control
Lansoprazole 30 mg twice daily plus bismuth 150 mg three times daily plus tetracycline 500 mg three times daily plus metronidazole 400 mg three times daily for 14 days.
Outcome
Primary: eradication on carbon-13 urea breath test. Secondary: side effects, stopping treatment because of side effects, and taking at least 80% of doses.
Follow-up Period
Breath test at 8-week follow-up (about 6 weeks after finishing therapy).
Results
| Outcome | Key finding |
|---|---|
| Eradication (primary) | 90.6% vs 89.3% (difference 1.2 percentage points; 95% range −5.7 to 8.2); met “not worse by >10 points” criterion. |
| Any treatment-related side effect | 10.9% vs 45.7%; 34.8 fewer per 100 treated (number needed to treat: 3 to prevent 1 side effect). |
| Stopped treatment because of side effects | 0.0% vs 8.6% (number needed to treat: 12 to prevent 1 stop). |
| Took at least 80% of doses | 96.0% vs 87.4% (number needed to treat: 12 for 1 additional patient to complete adequately). |
Eradication results were reported for patients who took at least one dose and returned for breath testing. This was a noninferiority trial with a prespecified 10 percentage-point margin.
Limitations
Single-center and open-label design may limit generalizability and may bias side-effect reporting. No antibiotic resistance testing was done. The 10-point noninferiority margin may be considered wide.
Funding
Beijing municipal science foundation; Peking University First Hospital youth clinical research grant.
Clinical Application
For rescue treatment after prior failure, consider 14-day vonoprazan plus tetracycline to reduce side effects and improve completion without lowering eradication success.
Discussion
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In this open-label noninferiority RCT, vonoprazan–tetracycline (VT) dual therapy vs bismuth quadruple therapy (BQT) achieved H pylori eradication 90.6% vs 89.3% (difference 1.2%, 95% CI −5.7% to 8.2%) with fewer TEAEs (10.9% vs 45.7%)—how do design limits and local resistance patterns affect validity and whether you’d change rescue therapy? The trial was a noninferiority RCT with a prespecified 10% noninferiority margin. In the mITT analysis, eradication (VT − BQT) was +1.2% with a 95% CI of −5.7% to +8.2%. Which interpretation is most appropriate?