Meta-analysis: High-dose vs. low-dose metronidazole-containing therapies for Helicobacter pylori eradication treatment

Objective: The purpose of this study was to evaluate the efficacy of high dose of metronidazole in the treatment of Helicobacter pylori (H. pylori) infection. Methods: Studies were identified from databases (Pubmed, Embase, Cochrane Library, ClinicalTrials.gov) searched from January 1990 to September 2017 using a battery of keywords. We included randomized controlled trials (RCTs) of H. pylori treatment comparing the high-dose and low-dose metronidazole-containing therapies (high-dose and low-dose therapies). Two reviewers independently selected studies, extracted relevant data and assessed study quality. A meta-analysis was performed by using Review Manager 5.3. Dichotomous data were pooled to obtain the relative risk (RR) of the eradication rate, with 95% confidence intervals (CIs). Results: Four randomized controlled trials, a total of 612 patients with a diagnosis of H. pylori infection were included. Overall the meta-analysis showed that both high-dose and low-dose therapies achieved similar efficacy of intention-to-treat (ITT) eradication rate 82% vs. 76%, RR 1.12 (95%CI: 0.96 to 1.30), P = 0.15, and adherence 94% vs. 94%, RR 1.00 (95%CI: 0.97 to 1.04), P = 0.81, but side effects were more likely in high-dose therapies [32% vs. 17%, RR 1.84 (95%CI: 1.17 to 2.88), P = 0.008]. In subgroup analysis, increasing the dose of metronidazole enhanced eradication rates in areas with high metronidazole resistance [74% vs 52%, RR 1.40 (95%CI: 1.08 to 1.82), P = 0.01] and in individuals with metronidazole-resistant strains [71% vs. 46%, RR 1.50 (95%CI: 1.02 to 2.19), P = 0.04]. Conclusions: Both high-dose and low-dose therapies can achieve similar eradication rates and adherence and generally low-dose therapies cause fewer side effects. In populations with high metronidazole resistance, high dose of metronidazole can increase the eradication rates of H. pylori infection.