Failure of a 1‐day high‐dose quadruple therapy for cure of Helicobacter pylori infection

Background: The optimal duration of treatment for eradication of Helicobacter pylori has still to be defined. A 1‐day high‐dose quadruple therapy with a combination of amoxycillin (or tetracycline), metronidazole, a bismuth salt and a proton pump inhibitor has led to eradication rates of 57–77%. In view of the high frequency of metronidazole‐resistant strains of H. pylori in Europe, we hypothesized that by using clarithromycin in place of metronidazole and by increasing the dose of proton pump inhibitor, the efficacy of a 1‐day high‐dose quadruple therapy could be improved. Methods: Patients were randomized to receive either amoxycillin 1000 mg b.d., clarithromycin 500 mg b.d. and lansoprazole 30 mg b.d. for 7 days, or amoxycillin 2000 mg q.d.s., clarithromycin 500 mg q.d.s., lansoprazole 30 mg t.d.s. and bismuth subcitrate 240 mg q.d.s. for 1 day. Results: It was originally intended to include 100 patients. The first planned interim analysis performed after follow‐up was completed for 30 patients revealed H. pylori eradication rates of 80% (12/15) in the 7‐day triple therapy group and 20% (3/15) in the 1‐day quadruple therapy group, the difference being highly significant (P = 0.003). Because the efficacy of the 1‐day treatment was so low, the study was stopped for ethical reasons. Eleven patients who failed with the 1‐day treatment were re‐treated with the 7‐day triple therapy: the eradication rate was 91% (10/11). Conclusions: One‐day high‐dose quadruple therapy with amoxycillin, clarithromycin, lansoprazole and bismuth subcitrate is dramatically less effective than the classic 7‐day triple therapy with the same antibiotics.