Systematic review and meta-analysis: full- vs. half-dose anti-microbials in clarithromycin-based regimens for Helicobacter pylori eradication.

BACKGROUND: Half-dose regimens may be equally effective but associated with diminished adverse events (AE) than standard-dose regimens. AIM: To assess efficacy and safety of full- vs. half-dose clarithromycin in the treatment of H. pylori. METHODS: Medline, EMBASE and PubMed databases were searched for randomised controlled trials (RCTs) that meet eligibility criteria. Only parallel group RCTs with ≥ 2 arms were eligible. Studies comparing triple, quadruple or sequential therapy for 7-14 days were selected. Regimens had to contain the same drug combination, differing only in dosage; the comparison of full- vs. half-dose clarithromycin was required, regardless if other drugs were dose-reduced or not. Data extraction was performed for primary outcome [eradication by intent-to-treat (ITT) and per-protocol (PP) analyses] and secondary outcome (AE). RESULTS: A total of 1622 articles were identified, of which 19 studies were eligible. Overall, eradication was achieved in 82.5% of half-dose (n = 2115) vs. 83.4% of full-dose recipients (n = 2109) on ITT (87.1% vs. 88.4% on PP respectively). Pooled relative risk in the half- vs. full-dose regimen was 0.98 (95% CI: 0.95-1.02) on ITT and 0.99 (95% CI: 0.97-1.01) on PP by the random effects model. Heterogeneity was significant (chi-squared statistic P = 0.05, I(2) = 37%). AE were reported in 29.3% of half- vs. 44.0% of full-dose recipients [pooled RR 0.67 (95% CI: 0.60-0.75)]. Pre-planned subgroup analyses of dose modification, sample size, study origin and treatment duration, as well as sensitivity analysis showed no significant differences between arms. CONCLUSION: A half-dose clarithromycin-based regimen is equally effective yet better tolerated than its full-dose counterpart in the treatment of H. pylori.