BISMUTH-BASED COMBINATION THERAPY FOR HELICOBACTER-PYLORI-ASSOCIATED PEPTIC-ULCER DISEASE (METRONIDAZOLE FOR ERADICATION, RANITIDINE FOR PAIN)

Objectives: 180 Helicobacter pylori-positive patients with peptic ulce r disease were randomly allocated to double-blind placebo-controlled t reatment with one of four anti-H. pylori regimens consisting of bismut h subnitrate suspension (B), oxytetracycline (OT), metronidazole (M)/m etronidazole placebo, or ranitidine (R)/ranitidine placebo. Methods: R egimen 1: B 150 mg q.i.d., OT 500 mg q.i.d., M 400 mg t.i.d. for 10 da ys and R 300 mg b.i.d. for 4 wk. Regimen 2: same as regimen 1 except r anitidine. Regimen 3: same as regimen 1 except metronidazole. Regimen 4: same as regimen 1 except metronidazole and ranitidine. Gastroscopy and C-14-urea breath test were performed 4 wk after cessation of thera py, and breath test six months after cessation. Results: According to intention-to-treat analysis, H. pylori eradication rates were 96%, 91% , 20%, and 9% with regimens 1, 2, 3, and 4, respectively. Comparing re gimens 1+2 with 3+4, the eradication rates with and without metronidaz ole were 93% and 14%, respectively (p < 0.0001). Metronidazole increas ed the occurrence of diarrhea and abdominal pain. Comparing regimens 1 +3 with 2+4 ranitidine did not influence H. pylori eradication (58% wi th and 50% without ranitidine; p = 0.37) or ulcer healing (93% with an d 90% without ranitidine; p = 0.72) significantly, but reduced the occ urrence of pain (p < 0.01). Six months after treatment, three patients who were H. pylori negative at 4 wk had become positive. These three had all received metronidazole placebo. H. pylori status remained nega tive in the other 85 patients. Conclusions: H. pylori eradication with this triple therapy is critically dependent on metronidazole. Adding ranitidine reduces the occurrence of abdominal pain during such therap y.