Sequential therapy or triple therapy for Helicobacter pylori infection: systematic review and Meta-analysis of randomized controlled trials in adults and children.

Background: Eradication rates with triple therapy (TT) for H. pylori infection have declined to unacceptable levels. Sequential therapy (ST) is a novel treatment that has shown promise in several controlled trials. Objective: To assess the efficacy of ST compared to TT, in adults and children by performing a systematic review and meta-analysis. Methods: Cochrane Trial Register (until Issue 4, 2008), MEDLINE (1966 – October 21st 2008), EMBASE (1980- October 21st 2008) and abstracts from the major US, European and Asian gastroenterology conferences. Randomized controlled trial (RCT) or a controlled clinical trial (CCT) with a parallel group design comparing the ST with a TT lasting at least 7 days. Results: 10 RCTs enrolled 3006 adult patients and the OR for eradication of H. pylori with ST compared to TT was 2.99 (95% CI: 2.47 to 3.62), giving a NNT of 6 (95% CI: 5 to 7) favouring ST. There was no publication bias. The OR for eradication with ST compared to 10-day TT was 2.92 (95% CI: 1.95 to 4.38), yielding a NNT of 8 (95% CI: 6 to 12), favouring ST. In patients with clarithromycin resistance, the OR for eradication with ST was 10.21 (95% CI: 3.01 to 34.58) compared to TT, but the numbers studied are small. 3 RCTs enrolled 260 children and the OR for eradication was 1.98 (95% CI 0.96 to 4.07). There was no difference in the rate of side effects between the ST and the TT (OR 1.01; 95% CI 0.78 to 1.30). Conclusions Sequential therapy appears to be better than triple therapy in the eradication of H. pylori. This is a promising therapy but needs further trials in other European countries and North America before it can be recommended as first line.