Evaluation of short-term low-dose triple therapy for the eradication of Helicobacter pylori by factorial design in a randomized, double-blind, controlled study

Aliment Pharmacol Ther. 1998 May;12(5):439-45. doi: 10.1046/j.1365-2036.1998.00330.x.


Background: Studies demonstrating the efficacy of short-term low-dose triple therapies including omeprazole (O), clarithromycin (C) and a nitroimidazole (tinidazole, T) for Helicobacter pylori eradication have largely been open and uncontrolled, and have not assessed antibiotic sensitivity. Simpler regimens using the component drugs have not been evaluated.

Aim: To evaluate the OCT regimen in a randomized, controlled trial, testing for pre- and post-treatment antibiotic resistance and comparing, in a factorial design, the OCT regimen with simpler combinations of its components.

Methods: One hundred and twenty-eight patients (68 males, 60 females, age 22-80 years, mean 53 years) with H. pylori gastritis were randomly assigned to one of the following four treatment groups: (C) clarithromycin 250 mg b.d.; (OC) omeprazole 20 mg o.d. + clarithromycin 250 mg b.d.; (CT) clarithromycin 250 mg b.d. + tinidazole 500 mg b.d.; (OCT) omeprazole 20 mg q.d.s. + clarithromycin 250 mg b.d. + tinidazole 500 mg b.d. The drugs were administered for 1 week. Medical interview, upper gastrointestinal endoscopy (with four antral and four corpus biopsies) and the 13C-urea breath test were carried out for all patients prior to and 4 weeks after treatment. Biopsy specimens were used for the urease test, histology, and culture and sensitivities.

Results: All but one patient completed treatment. Side-effects were rare and mild in all groups. The eradication rate was 93.8% in group OCT, 59.4% in group CT, 31.3% in group OC and 6.3% in group C. Pre-treatment metronidazole resistance was 12.8%, clarithromycin 1.1% and, to both antibiotics, 2.1%. In patients with pre-treatment metronidazole resistance, the eradication rate was 75% in group OCT and 33% in group CT. Post-treatment resistance to clarithromycin was induced in 28.5% of the failures in group C, but in none of group OC. Resistance to both antibiotics occurred in 22.2% of the failures in group CT and in none of group OCT.

Conclusions: (i) The high efficacy of the OCT regimen is proved and each of the individual components of the regimen is essential to the result, possibly via a synergistic effect. (ii) Pre-treatment metronidazole resistance is scarcely relevant to the outcome. (iii) Acquired resistance is essentially nil if omeprazole is part of the regimen.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents / therapeutic use*
  • Anti-Ulcer Agents / therapeutic use*
  • Clarithromycin / therapeutic use*
  • Double-Blind Method
  • Drug Resistance, Microbial
  • Drug Therapy, Combination
  • Female
  • Helicobacter Infections / drug therapy*
  • Helicobacter Infections / microbiology
  • Helicobacter pylori* / drug effects
  • Humans
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Omeprazole / therapeutic use*
  • Research Design
  • Tinidazole / therapeutic use*


  • Anti-Bacterial Agents
  • Anti-Ulcer Agents
  • Tinidazole
  • Clarithromycin
  • Omeprazole