Ten RCTs (n=2,747) were included in the review. One trial scored the maximum 5 points for methodological quality, four trials scored 3 points, three trials scored 2 points and two trials scored one point. Three RCTs failed to describe the randomisation process, six RCTs were open label, only one RCT was reported to be double-blind, and four RCTs failed to adequately describe withdrawals.
Pooled crude H. pylori eradication rates (10 RCTs, n=2,747) for sequential therapy were 93.4% (95% CI: 91.3, 95.5, n=1363) and for standard triple therapy were 76.9% (95% CI: 71, 82.8, n=1,384). This resulted in a relative risk reduction of 71% (95% CI: 64, 77) and an absolute risk reduction of 16% (95% CI: 14, 19) in favour of sequential therapy. There was no evidence of statistical heterogeneity (I2 = 0%).
Similar results were reported in sub group analyses with sequential therapy appearing superior to standard therapy when stratified by trial quality, ulcer healing, diagnosis (peptic ulcer disease, nonulcer disease), patient age, smoking status, resistance to clarithromycin, imidazoles or both, duration of triple therapy and method of diagnosis.
Inspection of the funnel plot showed evidence of significant publication bias in favour of sequential therapy. Neither the Begg or Egger test showed any significant evidence of publication bias.
Adverse events (7 RCTs): Both treatments reported similar adverse events. The most common adverse events were diarrhoea, abdominal pain and glossitis.