Efficacy of metronidazole as second-line drug for the treatment of Helicobacter pylori infection in the Japanese population: A multicenter study in the Tokyo Metropolitan Area

Background: With the increase in the frequency of clarithromycin-resistant Helicobacter pylori (H. pylori), there is rising concern about the decline of the eradication rate of this infection following treatment. The Tokyo Hp Study Group examined the eradication rate in response to a second-line regimen consisting of proton pump inhibitor (PPI), amoxicillin, and metronidazole by conducting a multicenter study in the Tokyo Metropolitan Area. Materials and Methods: Two hundred and twenty-eight patients with H. pylori infection, in whom the first-line therapy with a PPI, amoxicillin, and clarithromycin administered for 1 week had failed to eradicate the infection, were enrolled in this study. These cases were randomly assigned to one of the two second-line regimens containing metronidazole (PPI/AM₅₀₀ or PPI/AM₇₅₀) administered for 1 week. ¹³C-urea breath test was performed as a diagnostic method test for H. pylori infection not earlier than 8 weeks after the second-line therapy. Results: Intention-to-treat (ITT) and per-protocol (PP) analyses revealed an eradication rate of 87.6 and 90.6%, respectively, following PPI/AM₅₀₀ treatment, and 86.9 and 88.6%, respectively, following PPI/AM₇₅₀ treatment. Neither analysis revealed any significant difference in the eradication rate between PPI/AM₅₀₀ and PPI/AM₇₅₀ (p = .876 and .621, respectively). According to ITT and PP analyses, the eradication rates following treatment with PPI/AM₅₀₀ were 85.2 and 88.5% with the use of lansoprazole, 62.5 and 62.5% with the use of omeprazole, and 93.2 and 96.5% with the use of rabeprazole, respectively. There was a significant difference in the eradication rates between PPI (omeprazole)/AM₅₀₀ and PPI (rabeprazole)/AM₅₀₀. In the case of PPI/AM₇₅₀, the corresponding eradication rates were 84.8 and 87.0% with the use of lansoprazole, 92.9 and 92.9% with the use of omeprazole, and 92.9 and 92.9% with the use of rabeprazole, respectively. There were no significant differences in the eradication rates obtained with the use of the three PPIs. Conclusions: Both PPI/AM₅₀₀ and PPI/AM₇₅₀ administered for 1 week appeared to be highly effective second-line regimens for the treatment of H. pylori infection in Japanese patients. From the viewpoint of adverse events, PPI/AM₅₀₀ appeared to be safe compared with PPI/AM₇₅₀.