The HOMER study: The effect of increasing the dose of metronidazole when given with omeprazole and amoxicillin to cure Helicobacter pylori infection

Background. Helicobacter pylori eradication with omeprazole, amoxicillin, a nd metronidazole is both effective and inexpensive. However, eradication ra tes with different dosages and dosing vary, and data on the impact of resis tance are sparse. In this study, three different dosages of omeprazole, amo xicillin, and metronidazole were compared, and the influence of metronidazo le resistance on eradication was assessed. Methods. Patients (n = 394) with a positive H. pylori screening test result and endoscopy-proven duodenal ulcer in the past were enrolled into a multi center study performed in four European countries and Canada. After baselin e endoscopy, patients were randomly assigned to treatment for 1 week with e ither omeprazole, 20 mg twice daily, plus amoxicillin, 1,000 mg twice daily , plus metronidazole, 400 mg twice daily (low M); or omeprazole, 40 mg once daily, plus amoxicillin, 500 mg three times daily, plus metronidazole, 400 mg three times daily (medium M); or omeprazole, 20 mg twice daily, plus am oxicillin, 1,000 mg twice daily, plus metronidazole, 800 mg twice daily (hi gh M). H. pylori status at entry was assessed by a C-13 urea breath test an d a culture. Eradication was defined as two negative C-13-urea breath test results 4 and 8 weeks after therapy. Susceptibility testing using the agar dilution method was performed at entry and in patients with persistent infe ction after therapy. Results. The eradication rates, in terms of intention to treat (ITT) (popul ation n = 379) (and 95% confidence interval [CI]) were as follows: low M 76 % (68%, 84%), medium M 76% (68%, 84%), and high M 83% (75%, 89%). By per-pr otocol analysis (population n = 348), the corresponding eradication rates w ere: low M 81%, medium M 80%, and high M 85%. No H. pylori strains were fou nd to be resistant to amoxicillin. Prestudy resistance of H. pylori strains to metronidazole was found in 72 of 348 (21%) of the cultures at entry (ra nge, 10%-39% in the five countries). The overall eradication rate in prestu dy metronidazole-susceptible strains was 232 of 266 (87%) and, for resistan t strains, it was 41 of 70 (57%; P < 001). Within each group, the results w ere as follows (susceptible/resistant): low M, 85%/54%; medium M, 86%/50%; and high M, 90%/75%. There were no statistically significant differences am ong the treatment groups. 23 strains susceptible to metronidazole before tr eatment were recultured after therapy failed; 20 of these had now developed resistance. Conclusions. H. pylori eradication rates were similar (approximately 80%) w ith all three regimens. Metronidazole resistance reduced efficacy; increasi ng the dose of metronidazole appeared not to overcome the problem or signif icantly improve the outcome. Treatment failure was generally associated wit h either prestudy or acquired metronidazole resistance. These findings are of importance when attempting H. pylori eradication in communities with hig h levels of metronidazole resistance.