Rescue Therapy for Helicobacter pylori Eradication: A Randomized Non-Inferiority Trial of Amoxicillin or Tetracycline in Bismuth Quadruple Therapy

OBJECTIVES: To compare the efficacy and safety of bismuth-containing quadruple therapy with tetracycline or amoxicillin for rescue treatment of Helicobacter pylori. METHODS: The study was a non-inferiority trial of H. pylori eradication with at least two previous treatment failures. Subjects were randomized to receive 14-day therapy with b.i.d. lansoprazole 30 mg and bismuth 220 mg, plus metronidazole 400 mg q.i.d and amoxicillin 1 g t.i.d (amoxicillin group) or tetracycline 500 mg q.i.d (tetracycline group). Antimicrobial susceptibility was assessed by the agar-dilution method. Primary outcome was H. pylori eradication at 6 weeks after treatment. RESULTS: In all, 312 subjects were randomized, 13 were lost to follow-up; 29 violated the protocol. The intention-to-treat, per-protocol, and modified intention-to-treat eradication rates were (amoxicillin) 88.5% (138/156, 95% confidence interval (CI) 83.4-93.5%), 93.7% (133/142, 95% CI 89.7-97.7%), and 92.6% (138/149, 95% CI 88.4-96.8%). With tetracycline, they were 87.2% (136/156, 95% CI 81.9-92.4%), 95.3% (122/128, 95% CI 91.7-99.0%), and 90.7% (136/150, 95% CI 86.0-95.3%). Amoxicillin-, tetracycline-, and metronidazole-resistant rates were 8.3, 1.0, and 87.8%, respectively. Non-inferiority was confirmed (P < 0.025). Metronidazole resistance did not affect the efficacy of either therapy. Compliance was greater and moderate and severe adverse events were less among those receiving amoxicillin than those receiving tetracycline. CONCLUSIONS: The novel bismuth-containing quadruple therapy with metronidazole and amoxicillin is an alternative to classical bismuth quadruple therapy for H. pylori rescue treatment as it provides similar eradication with superior safety and compliance.