Original Article
Randomized controlled trial: PPI-based triple therapy containing metronidazole versus clarithromycin as first-line treatment for Helicobacter pylori in adolescents and young adults in Japan

https://doi.org/10.1016/j.jiac.2018.02.013Get rights and content

Abstract

Background/Aims

Treating Helicobacter pylori infection in young people is effective for preventing gastric cancer. This study compares the efficacy of triple therapies in adolescents and young adults in Japan.

Methods

This multicenter, randomized trial was conducted between February 2012 and March 2015. Infected participants were stratified into adolescents (13–19 years) and young adults (20–39 years). They were randomly assigned to a clarithromycin based (PAC) or metronidazole based (PAM) triple therapy for 1 week.

Results

Overall, 137 and 169 participants received the PAC and PAM treatments, respectively. In adolescents, the H. pylori eradication rates were 60.5% and 63.4% for PAC, and 98.3% and 100% for PAM in the intention-to-treat (ITT) and per-protocol (PP) analyses, respectively. In young adults, the eradication rates were 67.0% and 66.7% for PAC, and 95.5% and 96.3% for PAM in ITT and PP analyses, respectively. The eradication rate of PAM was significantly higher than that of PAC in both strata. No severe adverse events were observed.

Conclusion

In Japan, PAM may be selected as a first-line treatment for young people with H. pylori if antibiotic susceptibility tests cannot be performed.

Introduction

Helicobacter pylori was first discovered in 1983 [1], and the International Agency for Research on Cancer of the World Health Organization classified H. pylori as a definite carcinogen in 1994 [2]. H. pylori in the East Asia area, including Japan, shows a clear pathogenesis [3]. In Japan, gastric cancer is one of the most common cancers, and the annual number of deaths from gastric cancer is approximately 45,000. H. pylori infection causes gastritis, which leads to atrophic gastritis and gastric cancer [4]. In a prospective study, H. pylori-infected patients developed gastric cancer, whereas few uninfected patients developed gastric cancer [5]. In addition, a very low prevalence of H. pylori-negative gastric cancer was reported in the Japanese population [6], [7]. Several studies have demonstrated that the treatment of H. pylori infection in the elderly or in patients with gastric atrophy makes the incidence of gastric cancer approximately a half [8], [9]. However, eradication therapy in younger patients or in those with mild gastric mucosal atrophy is more effective for eliminating gastric cancer [10]. Therefore, to prevent gastric cancer, the treatment of H. pylori in young people is essential in areas such as Japan where gastric cancer is prevalent. A screen-and-treat strategy for H. pylori infection has been initiated for adolescents and young adults living in specific local areas with the aim of preventing gastric cancer, and we expect it will be implemented across Japan [11].

In the Japanese national health insurance system, proton pump inhibitor (PPI)-based triple therapy containing clarithromycin (CAM) and amoxicillin (AMPC) (PAC) is used as first-line treatment for adult patients who are diagnosed as H. pylori gastritis by upper endoscopy. A PPI-based triple therapy containing metronidazole (MNZ) and AMPC (PAM) is used as a second-line treatment. The prevalence of CAM-resistant H. pylori strain is increasing [12], [13], [14], and the successful treatment rate of the PPI-based CAM containing regimen has decreased, particularly in children and adolescents [14]. Therefore, it is desirable to conduct antibiotic susceptibility tests before treatment. In the ‘screen-and-treat of H. pylori’ strategy of young people, however, it is difficult to perform upper endoscopy and conduct antibiotic susceptibility tests for all patients who receive eradication treatment. Therefore, the aim of the present study was to compare the efficacy and tolerability of the two PPI-based triple therapies for H. pylori-infected adolescents and young adults for whom an antibiotics susceptibility test was not performed.

Section snippets

Patients and methods

The protocol of this study was reviewed and approved by the ethics committee of Hokkaido University Hospital and that of each of the thirty participating institutions. Written informed consent was obtained from all participants or their parents or guardians if they were minors (under 20 years old).

Participants' baseline characteristics

The flowchart of participants is shown in Fig. 1. We enrolled 1064 participants in this study, of whom 727 did not have H. pylori infection, as assessed by negative urine and/or serum antibody tests. No invalid result was observed in this study. Three hundred and thirty-seven participants were diagnosed with H. pylori infection. Of these, 152 patients were randomly assigned by computer to the PAC group, and 185 were assigned to the PAM group. From the PAC and PAM groups, 15 and 16 patients were

Discussion

Two PPI-based triple treatments were approved by the Japanese National Health Insurance system for adults in Japan. This is the first randomized trial comparing the two treatments in asymptomatic adolescents and young adults in Japan. The results showed that the PAM regimen with MNZ had significantly higher eradication rates than the PAC regimen with CAM; and the successful eradication rate of PAC was too low to support its use for first-line treatment. Surprisingly, the successful eradication

Conflicts of interest

Mabe K reports a personal lecture fee (Takeda Pharmaceutical Co and Ltd. and Eisai Co. LTD). Okuda M also reports a personal lecture fee (Otsuka Pharmaceutical Co., Ltd. and Eisai Co. LTD). Asaka M and Mabe K belong to the donation-funded Department of Eizai Co. Ltd., at Cancer Preventive Medicine, Hokkaido University Graduate School of Medicine. Kikuchi S, Amagai K, and Yoshimura R declare no conflicts of interest.

ICMJE statement

All authors meet the ICMJE authorship criteria.

Acknowledgment

We thank J. Ludovic Croxford, PhD, from Edanz Group (www.edanzediting.com/ac) for editing a draft of this manuscript.

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