Optimized sequential therapy vs 10- and 14-d concomitant therapy for eradicating Helicobacter pylori: A randomized clinical trial.

Abstract

A cure for Helicobacter pylori (H. pylori) remains a problem of global concern. The prevalence of antimicrobial resistance is widely rising and becoming a challenging issue worldwide. Optimizing sequential therapy seems to be one of the most attractive strategies in terms of efficacy, tolerability and cost. The most common sequential therapy consists of a dual therapy [proton-pump inhibitors (PPIs) and amoxicillin] for the first period (5 to 7 d), followed by a triple therapy for the second period (PPI, clarithromycin and metronidazole). PPIs play a key role in maintaining a gastric pH at a level that allows an optimal efficacy of antibiotics, hence the idea of using new generation molecules. To compare an optimized sequential therapy with the standard non-bismuth quadruple therapies of 10 and 14 d, in terms of efficacy, incidence of adverse effects (AEs) and cost. This open-label prospective study randomized 328 patients with confirmed H. pylori infection into three groups (1:1:1): The first group received quadruple therapy consisting of twice-daily (bid) omeprazole 20 mg, amoxicillin 1 g, clarithromycin 500 mg and metronidazole 500 mg for 10 d (QT-10), the second group received a 14 d quadruple therapy following the same regimen (QT-14), and the third group received an optimized sequential therapy consisting of bid rabeprazole 20 mg plus amoxicillin 1 g for 7 d, followed by bid rabeprazole 20 mg, clarithromycin 500 mg and metronidazole 500 mg for the next 7 d (OST-14). AEs were recorded throughout the study, and the H. pylori eradication rate was determined 4 to 6 wk after the end of treatment, using the 13C urea breath test. In the intention-to-treat and per-protocol analysis, the eradication rate was higher in the OST-14 group compared to the QT-10 group: (93.5%, 85.5% P = 0.04) and (96.2%, 89.5% P = 0.03) respectively. However, there was no statistically significant difference in eradication rates between the OST-14 and QT-14 groups: (93.5%, 91.8% P = 0.34) and (96.2%, 94.4% P = 0.35), respectively. The overall incidence of AEs was significantly lower in the OST-14 group (P = 0.01). Furthermore, OST-14 was the most cost-effective among the three groups. The optimized 14-d sequential therapy is a safe and effective alternative. Its eradication rate is comparable to that of the 14-d concomitant therapy while causing fewer AEs and allowing a gain in terms of cost.