Sequential therapy versus standard triple-drug therapy for Helicobacter pylori eradication: a randomized trial

Ann Intern Med. 2007 Apr 17;146(8):556-63. doi: 10.7326/0003-4819-146-8-200704170-00006.


Background: Antimicrobial resistance has decreased eradication rates for Helicobacter pylori infection worldwide.

Objective: To determine whether sequential treatment eradicates H. pylori infection better than standard triple-drug therapy for adults with dyspepsia or peptic ulcers.

Design: Randomized, double-blind, placebo-controlled trial.

Setting: Two Italian hospitals between September 2003 and April 2006.

Patients: 300 patients with dyspepsia or peptic ulcers.

Measurements: (13)C-urea breath test, upper endoscopy, histologic evaluation, rapid urease test, bacterial culture, and assessment of antibiotic resistance.

Intervention: A 10-day sequential regimen (40 mg of pantoprazole, 1 g of amoxicillin, and placebo, each administered twice daily for the first 5 days, followed by 40 mg of pantoprazole, 500 mg of clarithromycin, and 500 mg of tinidazole, each administered twice daily for the remaining 5 days) or standard 10-day therapy (40 mg of pantoprazole, 500 mg of clarithromycin, and 1 g of amoxicillin, each administered twice daily).

Results: The eradication rate achieved with the sequential regimen was significantly greater than that obtained with the standard treatment in the intention-to-treat analysis (89% vs. 77%; P = 0.0134; difference, 12% [95% CI, 3% to 20%]), the modified intention-to-treat analysis (91% vs. 78%; P = 0.0022; difference, 13% [CI, 5% to 21%]), and the per-protocol analysis (93% vs. 79%; P = 0.0013; difference, 14% [CI, 6% to 21%]). Sequential therapy was significantly more effective in patients with clarithromycin-resistant strains (89% vs. 29%; P = 0.0034). The incidence of major and minor side effects did not differ between therapy groups (17% in both groups). One patient (0.7%) in the standard therapy group discontinued treatment because of side effects.

Limitations: Follow-up was incomplete in 4.6% and 2.7% patients in the sequential therapy and standard therapy groups, respectively. The results may not be generalizable to other countries. Sequential therapy may be more effective because it includes 1 additional antibiotic (tinidazole) that is not contained in standard therapy.

Conclusions: Sequential therapy is statistically significant compared with standard therapy for eradicating H. pylori infection and is statistically significantly more effective in patients with clarithromycin-resistant strains. Side effects are similar with both treatment regimens and are rarely severe enough to cause discontinuation of therapy. registration number: NCT00403364.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / adverse effects
  • Anti-Ulcer Agents / administration & dosage*
  • Anti-Ulcer Agents / adverse effects
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Resistance, Bacterial
  • Drug Therapy, Combination
  • Dyspepsia / drug therapy*
  • Dyspepsia / microbiology
  • Female
  • Helicobacter Infections / drug therapy*
  • Helicobacter pylori*
  • Humans
  • Male
  • Middle Aged
  • Peptic Ulcer / drug therapy*
  • Peptic Ulcer / microbiology
  • Prospective Studies


  • Anti-Bacterial Agents
  • Anti-Ulcer Agents

Associated data