A randomized controlled comparison of three quadruple therapy regimens in a population with low Helicobacter pylori eradication rates

BACKGROUND AND AIM: We sought to compare the efficacy and tolerability of an omeprazole/clarithromycin/bismuth/tetracycline-based quadruple therapy to that of a ranitidine/metronidazole/bismuth/tetracycline-based quadruple therapy of 2 or 3 weeks duration in a population with a high prevalence of metronidazole-resistant Helicobacter pylori and low triple therapy eradication rates. METHODS: Two hundred and twenty-one patients who presented endoscopically proven duodenal ulcers and a positive rapid urease test were randomized to receive either: (i) omeprazole 20 mg b.i.d., clarithromycin 250 mg b.i.d., bismuth subcitrate 240 mg b.i.d. and tetracycline 500 mg b.i.d (OCBT) for 2 weeks; (ii) ranitidine 300 mg b.i.d., metronidazole 500 mg b.i.d, bismuth subcitrate 240 mg b.i.d. and tetracycline 500 mg b.i.d. (RMBT2) for 2 weeks; or (iii) ranitidine 300 mg b.i.d., metronidazole 500 mg b.i.d, bismuth subcitrate 240 mg b.i.d. and tetracycline 500 mg b.i.d. (RMBT3) for 3 weeks. Patients were interviewed 2 weeks after the completion of therapy to review compliance and side-effects. Eradication of H. pylori was assessed 8 weeks after the completion of therapy with the use of a 14C-urea breath test. RESULTS: The per-protocol eradication rate was significantly higher with OCBT (88%) than RMBT2 (73%) or RMBT3 (71%) (P<0.05). The intent-to-treat eradication rate was numerically higher with OCBT (80%) than RMBT2 (68%) or RMBT3 (68%), although this difference did not reach statistical significance (P=0.09). Per-protocol or intent-to-treat eradication rates were similar with RMBT2 and RMBT3. There were significantly greater side-effects with the RMBT2 regimen. CONCLUSIONS: The omeprazole/clarithromycin/bismuth/tetracycline-based quadruple therapy provides higher H. pylori eradication rates than the ranitidine/metronidazole/bismuth/tetracycline-based quadruple therapy when administered per protocol. The prolongation of the latter regimen from 2 to 3 weeks did not increase eradication rates.