Comparison of Three 7-Day Pantoprazole-Based Helicobacter pylori Eradication Regimens in a Mexican Population with High Metronidazole Resistance.

OBJECTIVE: To compare the efficacy and tolerability of three 7-day pantoprazole-based regimens to eradicate Helicobacter pylori in Mexican patients with peptic ulcer (PU) or non-ulcer dyspepsia (NUD).
BACKGROUND: Short-term therapeutic regimens based on a proton pump inhibitor (PPI) and two antibiotics have been recommended for the eradication of H. pylori. Resistance of H. pylori to metronidazole may adversely affect the efficacy of such regimens. PATIENTS AND METHODS: This was a single-centre, randomised, open-label, parallel-group study in which three groups of H. pylori-positive patients with PU or NUD were compared (n = 159; intention-to-treat population). Patients were randomised to receive a 7-day pantoprazole-based triple therapy for eradication of H. pylori. Patients received pantoprazole (P) 40mg twice daily in combination with either i) amoxicillin (A) 1000mg twice daily and clarithromycin (C) 500mg three times daily (PAC regimen, n = 51 patients), or ii) clarithromycin 500mg three times daily and metronidazole (M) 500mg three times daily (PCM regimen, n = 55 patients), or iii) amoxicillin 1000mg twice daily and metronidazole 500mg three times daily (PAM regimen, n = 53 patients). After completing eradication therapy, all PU patients were further treated with once-daily pantoprazole 40mg, either for another 3 weeks (patients with duodenal ulcer) or for another 7 weeks (patients with gastric ulcer), to ensure complete ulcer healing. At baseline examination, all patients underwent the (14)C-urea breath test and endoscopy; biopsy specimens were taken for histology, CLO-test, H. pylori culture and antibiotic susceptibility testing (agar dilution E-test). Eradication of H. pylori was assessed after all treatment with pantoprazole had been discontinued for at least 4 weeks, using the (14)C-urea breath test.
RESULTS: In the per-protocol population (n = 153), eradication was achieved in 81.3% (39/48) of patients receiving PAC, 66.0% (35/53) of PCM recipients, and 48.1 % (25/52) of those receiving PAM (p = 0.13 for PAC vs PCM and 0.001 for PAC vs PAM). In the intention-to-treat population, respective eradication rates were 76.5 (39/51), 63.6 (35/55) and 47.2% (25/53) [p = 0.22 for PAC vs PCM and 0.004 for PAC vs PAM]. Patient compliance was very good in all treatment groups. The main adverse event affecting 40% of all patients was a metallic taste, assessed as likely related to the antibiotics. Susceptibility to the three study antibiotics was determined for H. pylori isolates using the pretreatment biopsies from 103 patients. Resistance to metronidazole was present in 68.2% of patients and to clarithromycin in 24.3%. In 16.8% of patients, H. pylori isolates were resistant to both metronidazole and clarithromycin. In patient populations with H. pylori strains resistant to one or both of the antibiotics used in the respective treatment regimen, eradication rates were consistently lower than in those with susceptible H. pylori strains. However, these differences were not statistically significant, probably due to the small sample size.
CONCLUSIONS: The 7-day H. pylori eradication regimen with PAC was superior to PCM and PAM. This is probably due to the high resistance rate to metronidazole in the Mexican population. Thus, H. pylori eradication regimens that involve metronidazole cannot be recommended for Mexican patients. RESULTS from this study highlight the regional differences in efficacy of some well established H. pylori eradication regimens, and suggest that culture and susceptibility testing to define H. pylori resistance patterns in specific geographical areas may be indicated before recommending any particular eradication schedule.

RCT Entities:   Population Interventions Outcomes