Randomised trial of eradication of Helicobacter pylori before non-steroidal anti-inflammatory drug therapy to prevent peptic ulcers

Lancet. 1997 Oct 4;350(9083):975-9. doi: 10.1016/s0140-6736(97)04523-6.


Background: Helicobacter pylori infection is common in patients with peptic ulcers caused by the use of non-steroidal anti-inflammatory drugs (NSAIDs). But the pathogenic role of H pylori in this disease is controversial. We studied the efficacy of eradication of H pylori in the prevention of NSAID-induced peptic ulcers.

Methods: We recruited patients with musculoskeletal pain who required NSAID treatment. None of the patients had previous exposure to NSAID therapy. Patients who had H pylori infection but no pre-existing ulcers on endoscopy were randomly allocated naproxen alone (750 mg daily) for 8 weeks or a 1-week course of triple therapy (bismuth subcitrate 120 mg, tetracycline 500 mg, metronidazole 400 mg, each given orally four times daily) before administration of naproxen (750 mg daily). Endoscopy was repeated after 8 weeks of naproxen treatment or when naproxen treatment was stopped early because of bleeding or intractable dyspepsia. All endoscopic examinations were done by one endoscopist who was unaware of treatment assignment. The primary endpoint was the cumulative rate of gastric and duodenal ulcers.

Findings: 202 patients underwent endoscopic screening for enrolment in the trial, and 100 eligible patients were randomly assigned treatment. 92 patients completed the trial (47 in the naproxen group, 45 in the triple-therapy group). At 8 weeks, H pylori had been eradicated from no patients in the naproxen group and 40 (89%) in the triple-therapy group (p < 0.001). 12 (26%) naproxen-group patients developed ulcers: five had ulcer pain and one developed ulcer bleeding. Only three (7%) patients on triple therapy had ulcers, and two of these patients had failure of H pylori eradication (p = 0.01). Thus, 12 (26%) patients with persistent H pylori infection but only one (3%) with successful H pylori eradication developed ulcers with naproxen (p = 0.002).

Interpretation: Eradication of H pylori before NSAID therapy reduces the occurrence of NSAID-induced peptic ulcers.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Anti-Bacterial Agents / therapeutic use
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Bismuth / therapeutic use
  • Drug Administration Schedule
  • Duodenal Ulcer / chemically induced
  • Duodenal Ulcer / microbiology
  • Duodenal Ulcer / prevention & control*
  • Female
  • Helicobacter Infections / drug therapy*
  • Helicobacter pylori*
  • Humans
  • Male
  • Metronidazole / therapeutic use
  • Middle Aged
  • Naproxen / adverse effects
  • Naproxen / therapeutic use
  • Organometallic Compounds / therapeutic use
  • Prospective Studies
  • Stomach Ulcer / chemically induced
  • Stomach Ulcer / microbiology
  • Stomach Ulcer / prevention & control*
  • Tetracycline / therapeutic use


  • Anti-Bacterial Agents
  • Anti-Inflammatory Agents, Non-Steroidal
  • Organometallic Compounds
  • Metronidazole
  • Naproxen
  • Tetracycline
  • bismuth tripotassium dicitrate
  • Bismuth