Effect of Helicobacter pylori eradication on gastric cancer prevention in Korea: A randomized controlled clinical trial

Abstract

Despite the decreasing trend shown worldwide, considering the remaining high seroprevalence of H. pylori in the middle-aged population in the Republic of Korea (Korea) and the notable increase in gastric cancer (GC) incidence in specific age groups in the US, searching for and eradicating H. pylori may offer a great opportunity to reduce GC incidence dramatically. However, mass use of antibiotics that are necessary to eradicate the bacteria is likely to result in substantial overtreatment and may not be feasible. There are still some doubts about the effectiveness of H. pylori eradication in preventing GC and uncertainty about the eradication programs to maximize effectiveness and minimize possible adverse effects. A population-based double-blinded, randomized controlled clinical trial has therefore been proposed and being conducted in Korea to investigate the effectiveness of H. pylori eradication on GC prevention, addressing remaining unresolved issues. A total of 11,000 people between 40 and 65 years of age who are invited to the National Cancer Screening Program (NCSP) in Korea will be included in this study, among which about 60% of them are expected to beH. pylori positive. Eligible participants who agree to participate and sign informed consent undergo medical history and physical examination, and are administered a detailed lifestyle questionnaire. Blood (15 ml) is also collected in selected centers for ancillary studies. All participants undergo upper endoscopy and standard collection of gastric biopsies is made for histology and H. pylori diagnosis. Individuals who have already undergone their endoscopies as part of the NCSP or outside the NCSP scheme but could not be enrolled in the study prior to their gastroscopy are contacted for study participation and H. pylori status is determined with a breath test. H. pylori positive subjects are randomly assigned to either the treatment or placebo group in double-blind fashion. For those assigned to the treatment group, H. pylori eradication treatment with a 10-day course of bismuth-based quadruple therapy is provided while the others receive a placebo. Participants with no evidence of H. pylori infection or baseline chronic atrophic gastritis constitute the unexposed group to investigate natural history of the infection and GC precursors. All trial participants are followed up within the NCSP at least for 10 years to collect systematic information on medical conditions, in particular gastric cancer and causes of death. The primary endpoint of this trial is the incidence of histologically confirmed gastric adenocarcinoma. This study will be the first large clinical trial with endoscopic follow-up to provide comprehensive clinicopathological information about the H. pylori eradication effect on the GC incidence. Based on the results from this study, effective guideline for GC prevention could be established.