Eleven RCTs (eight full-text articles n=2,288 and three abstracts n=595) were included in the review: 1,338 patients received sequential therapy and 1,545 received standard triple therapy. One trial achieved a Jadad score of 5, six scored 3, three scored 2 and one scored 1.
Pooled analyses showed that sequential therapy was significantly more effective than 7-day standard therapy (RR 1.23, 95% CI 1.19 to 1.27; nine trials) and 10-day standard therapy (RR 1.16, 95% CI 1.10 to 1.23; four trials). There was no significant heterogeneity. Influence analysis was reported for comparison with 7-day standard therapy and produced a similar result. Inspection of funnel plot indicated no evidence of publication bias.
For patients with peptic ulcer dyspepsia, pooled analysis showed that sequential therapy was more effective than 7-day and 10-day standard therapy (RR 1.24, 95% CI 1.15 to 1.34; three trials), but there was significant heterogeneity (I2=77.1%, p=0.013). Heterogeneity was eliminated when the two regimens were analysed separately, but the superiority of sequential therapy remained.
For patients with non-ulcer dyspepsia, sequential therapy was more effective than the standard triple regimens (RR 1.26, 95% CI 1.19 to 1.33). There was no significant heterogeneity. Pooled risk ratios for studies in patients with clarithromycin and metronidazole resistance were 2.01 (95% CI 1.35 to 2.98; four trials) for clarithromycin and 2.07 (95% CI 1.30 to 3.31; three trials) for metronidazole. All results were unaffected in the sensitivity analyses.
Commonly reported adverse events were diarrhoea, glossitis, abdominal pain, nausea and vomiting. Frequency of these events (six trials) were similar across the study groups (8.4% for sequential therapy and 8.7% for 7-day triple regimens). Pooled analysis showed no significant differences between the groups. There was no significant heterogeneity.