Bismuth-based combination therapy for Helicobacter pylori-associated peptic ulcer disease (metronidazole for...

180 Helicobacter pylori-positive patients with peptic ulcer disease were randomly allocated to double-blind placebo-controlled treatment with one of four anti-H. pylori regimens consisting of bismuth subnitrate suspension (B), oxytetracycline (OT), metronidazole (M)/metronidazole placebo, or ranitidine (R)/ranitidine placebo.

Regimen 1: B 150 mg q.i.d., OT 500 mg q.i.d., M 400 mg t.i.d. for 10 days and R 300 mg b.i.d. for 4 wk. Regimen 2: same as regimen 1 except ranitidine. Regimen 3: same as regimen 1 except metronidazole. Regimen 4: same as regimen 1 except metronidazole and ranitidine. Gastroscopy and 14C-urea breath test were performed 4 wk after cessation of therapy, and breath test six months after cessation.

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 regimens 1+2 and 3+4, the eradication rates with and without metronidazole were 93% and 14%, respectively (p < 0.0001). Metronidazole increased the occurrence of diarrhea and abdominal pain. Comparing regimens 1+3 with 2+4 ranitidine did not influence H. pylori eradication (58% with and 50% without ranitidine; p = 0.37) or ulcer healing (93% with and 90% without ranitidine; p = 0.72) significantly, but reduced the occurrence 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 negative in the other 85 patients.

H. pylori eradication with this triple therapy is critically dependent on metronidazole. Adding ranitidine reduces the occurrence of abdominal pain during such therapy.