Ten-Day Sequential Treatment for H. pylori Eradication
Background: Cure rates of Helicobacter pylori infection with standard triple therapy are disappointingly low. A very effective, new sequential treatment schedule has recently been described. However, all studies published to date were performed in Italy; it is mandatory to confirm these results in other settings.
Aim: To assess the cure rate and the acceptability of a new sequential treatment regimen through a pilot study.
Methods: A hundred and thirty-nine patients (60% men, mean age 49.6 ± 15.7 yr) were recruited from six centers. H. pylori status was assessed by histology, urease test or urea breath test. Sequential regime consisted of a 10-day treatment including a proton pump inhibitor (PPI) b.d. plus amoxicillin 1 g b.d. for the first 5 days, followed by a PPI b.d. clarithromycin 500 mg b.d. and metronidazole 500 mg b.d for the next 5 days. Eradication was determined 8 wk after the end of treatment by urea breath test or histology. Eradication rates were calculated both per protocol and by intention-to-treat.
Results: Eradication was achieved in 117 out of 129 patients who returned for a follow-up test. The intention-to-treat eradication rate was thus 84.2% (95%CI: 77%-90%) and the per-protocol cure rate 90.7% (95%CI: 84%-95%). The treatment was well tolerated. Only 14 patients complained of mild side effects.
Conclusions: Sequential treatment seems highly effective for eradicating H. pylori.

The standard and most recommended treatment for the eradication of Helicobacter pylori, in all international guidelines, is triple therapy, using the combination of two antibiotics (clarithromycin plus amoxicillin or metronidazol) and a proton pump inhibitor (PPI) for at least 7 days. Unfortunately, a recent meta-analysis including over 53,000 patients showed that the eradication rate after a standard triple treatment is currently below 80%, meaning that eradication is not achieved in at least one out of five patients. Some European studies have reported even lower rates of eradication, with failure rates of 35-40%. The real benefit of a highly effective first-line therapy is much greater than the raw percentage data suggest. By improving the effectiveness of treatment, we reduce therapeutic failure, the need for new treatments, the use of a diagnostic test to confirm eradication and the loss of patients during follow up. Therefore, new strategies are required in order to improve first-line treatment.

One recent therapeutic innovation is sequential treatment, introduced in Italy around 7 yr ago. Strictly speaking, it is not a new approach, as it uses well-known drugs with approved indication for H. pylori eradication. However, the administration strategy is innovative and the sequential regimen has proved more effective than standard triple therapy administered either for 7 or 10 days. The same authors showed that sequential treatment was not affected by the characteristic risk factors for triple therapy failure such as the absence of the gene Cag A or smoking. Cure rates were also similar for nonulcer dyspepsia and ulcer patients. Clarithromycin resistance reduced sequential therapy efficacy although the decrease in eradication rates was far lower than in triple therapy. Furthermore, side effects were mild and infrequent, and not significantly different from those described with triple therapy.

So far, all the studies analyzing sequential therapy have been performed in Italy. Studies validating this strategy in different settings are mandatory before it can be widely recommended in clinical practice. We therefore decided to evaluate the effectiveness of the sequential treatment in our area in a pilot study under clinical practice conditions, and to assess patients' adherence to this therapeutic regimen and its side effects profile.