One week triple therapy for Helicobacter pylori: does high-dose clarithromycin confer additional benefit?

BACKGROUND: Clarithromycin, a new acid stable macrolide antibiotic with proven efficacy against Helicobacter pylori, has been widely incorporated into eradication regimens but its optimal dosage schedule remains controversial. The standard dose of clarithromycin is 250 mg twice daily.

METHODS: In a prospective study designed to evaluate the helicobactericidal efficacy, patient acceptability, and ulcer healing efficacy of a triple therapy regimen incorporating high dose clarithromycin, 100 consecutive patients with H. pylori-positive peptic ulcer received omeprazole 20 mg twice daily in combination with metronidazole 400 mg twice daily and clarithromycin 500 mg twice daily for seven days. H. pylori status was assessed before and at least 4 weeks after therapy by rapid urease test and histology. Adverse events and compliance were assessed by direct questioning.

RESULTS: Only two patients failed to attend for repeat endoscopy, leaving 98 evaluable patients. Of these, 94 were H. pylori-negative after therapy, giving an intention-to-treat eradication rate of 94% (95% confidence interval, 89%-99%). The ulcer healing rate was 92% (86%-98%), and ulcer healing was significantly associated with H. pylori eradication (p < 0.01). Adverse events were reported by 33% of patients of which nausea was the commonest (14%). Noncompliance with therapy was significantly associated with H. pylori treatment failure (p < 0.001).

CONCLUSIONS: Seven day triple therapy incorporating high dose clarithromycin effectively eradicates H. pylori and heals ulcers, but it is disadvantaged by a relatively high rate of adverse events. In view of these findings and the fact that no direct comparison to date has shown increased efficacy from high dose clarithromycin, we would recommend continued use of low dose clarithromycin when combined with omeprazole and a nitroimidazole.