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


METHODS
Randomized, double-blind, placebo-controlled trial.


METHODS
Two Italian hospitals between September 2003 and April 2006.


METHODS
300 patients with dyspepsia or peptic ulcers.


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


METHODS
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.


CONCLUSIONS
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. ClinicalTrials.gov registration number: NCT00403364.
Vaira
Dino
D
University of Bologna, Bologna, Italy. vairadin@med.unibo.it
Zullo
Angelo
A
Vakil
Nimish
N
Gatta
Luigi
L
Ricci
Chiara
C
Perna
Federico
F
Hassan
Cesare
C
Bernabucci
Veronica
V
Tampieri
Andrea
A
Morini
Sergio
S
D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000897:Anti-Ulcer Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D024881:Drug Resistance, Bacterial; D004359:Drug Therapy, Combination; D004415:Dyspepsia / Q000188:drug therapy* / Q000382:microbiology; D005260:Female; D016481:Helicobacter Infections / Q000188:drug therapy*; D016480:Helicobacter pylori; D006801:Humans; D008297:Male; D008875:Middle Aged; D010437:Peptic Ulcer / Q000188:drug therapy* / Q000382:microbiology; D011446:Prospective Studies
D000900:Anti-Bacterial Agents; D000897:Anti-Ulcer Agents