EVALUATION OF SHORT-TERM LOW-DOSE TRIPLE THERAPY FOR THE ERADICATION OF HELICOBACTER-PYLORI BY FACTORIAL DESIGN IN A RANDOMIZED, DOUBLE-BLIND, CONTROLLED-STUDY

Background: Studies demonstrating the efficacy of shortterm low-dose t riple therapies including omeprazole (O), clarithromycin (C) and a nit roimidazole (tinidazole, T) for Helicobacter pylori eradication have l argely been open and uncontrolled, and have not assessed antibiotic se nsitivity. Simpler regimens using the component drugs have not been ev aluated, Aim: To evaluate the OCT regimen in a randomized, controlled trial, testing for pre-and post-treatment antibiotic resistance and co mparing, in a factorial design, the OCT regimen with simpler combinati ons 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 treatmen t groups: (C) clarithromycin 250 mg b.d.; (OC) omeprazole 20 mg o.d. clarithromycin 250 mg b.d.; (CT) clarithromycin 250 mg b.d. + tinidaz ole 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 C-13-urea breath test were carried out for all patients prior to and 4 weeks after treatment. Biopsy spec imens were used for the urease test, histology, and culture and sensit ivities. Results: All but one patient completed treatment. Side-effect s 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. P re-treatment metronidazole resistance was 12.8%, clarithromycin 1.1% a nd, to both antibiotics, 2.1%, In patients with pre-treatment metronid azole resistance, the eradication rate was 75% in group OCT and 33% in group CT. Posttreatment resistance to clarithromycin was induced in 2 8.5% of the failures in group C, but in none of group OC. Resistance t o both antibiotics occurred in 22.2% of the failures in group CT and i n none of group OCT. Conclusions: (i) The high efficacy of the OCT reg imen 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 o f the regimen.