Helicobacter Pylori Eradication for Gastric Cancer Prevention in the General Population

Study Overview
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Brief Summary
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The aim of this study is to define the role of H. pylori eradication in the prevention of gastric cancer and its precursors in the context of a population-based endoscopic screening program.

Detailed Description
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Despite the decreasing incidence observed in the US and West European countries, gastric cancer is still an important global public health problem, especially in East Asian countries, where the burden of the disease is substantial. In the Republic of Korea, gastric cancer remains the leading cause of cancer in men and the fourth most common cancer in women. There is sufficient epidemiological and experimental evidence supporting a causal link between bacterial infection with H. pylori and gastric cancer development. However, evidence from clinical trials on the efficacy of H. pylori eradication with antimicrobial therapy to reduce the risk of gastric cancer is still limited. In addition, the beneficial or deleterious health impact of mass eradication at the population level has not been defined. In Korea, the prevalence of H. pylori infection in adults is still relatively high ( 60%, >16 years old), and despite important reductions in mortality attributed to the screening program, incidence of gastric cancer remains elevated. The investigators propose to conduct a randomized controlled clinical trial in Korea to evaluate the efficacy of H. pylori eradication to prevent gastric cancer incidence in different population subgroups including age and baseline gastric pathology. This study will be conducted in the context of the National Cancer Screening Program and the Korean Central Cancer Registry. The proposed study will be a collaborative investigation between the National Cancer Center, Korea and the International Agency for Research on Cancer of the World Health Organization.

Official Title
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Effect of Helicobacter Pylori Eradication on Gastric Cancer Prevention in Korea: a Randomized Controlled Clinical Trial

Conditions
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Gastric Cancer, Helicobacter Pylori Infection

Intervention / Treatment
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* Drug: 10-day bismuth-based quadruple therapy
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women aged 40-65 who are invited to participate in the National Cancer Screening Program and receive upper endoscopy Willingness to sign an informed consent form Good health, as determined by medical history and physical examination at enrollment Exclusion Criteria: Personal history of gastric cancer Family history of gastric cancer in a first degree relative Diagnosis and active treatment for other organ cancer except carcinoma in situ within 5 years Current treatment for serious medical condition which could hinder participation (such as liver cirrhosis, renal failure, pulmonary dysfunction including COPD or asthma, or uncontrolled infection) Inadequate cardiovascular function including (a) New York Heart Association class III or IV heart disease, (b) unstable angina or myocardial infarction history, (c) history of significant ventricular arrhythmia requiring medication with antiarrhythmics, and (d) history of cerebrovascular accident Requirement for therapeutic anticoagulant therapy, aspirin Gastric resections due to benign disease H. pylori eradication therapy history Mental incompetence to understand and sign informed consent Alcoholism, drug abuse Serious chronic diseases according to the evaluation of the study physician Presence of a contraindication to the use of eradication treatment regimens Inability to provide an informed consent Pregnant or lactating women Treatment required due to peptic ulcer, gastric cancer or esophageal cancer identified during the endoscopic examination

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Intervention group<br>10-day bismuth-based quadruple therapy for H. pylori positive subjects | Drug: 10-day bismuth-based quadruple therapy<br>* Bismuth 300 mg (4 times a day), lansoprazole 30 mg (twice a day), metronidazole 500 mg (3 times a day), and tetracycline 500 mg (4 times a day) for 10 days<br>* Other names: Bismuth-based quadruple therapy;|
| Placebo Comparator: Placebo group<br>Placebo for H. pylori positive subjects | Other: Placebo<br>* Placebo for bismuth-based quadruple therapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of gastric cancer between the intervention and placebo groups | Histologically confirmed gastric adenocarcinoma stage 1A or more advanced defined at endoscopy or through cancer registry | Up to 10 years After H. pylori eradication | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of gastric dysplasia | Diagnosis of histologically confirmed gastric dysplasia | Up to 10 years After H. pylori eradication | 
| Occurrence of adverse events caused by antibiotic treatment | Solicited/unsolicited adverse events | During 10 days of H. pylori eradication, and Up To 1 month after the treatment completion | 
| Incidence and mortality from other medical conditions such as obesity, diabetes, circulatory diseases, oesophageal diseases as well as other cancers and cognitive impairment | Assessed through record linkage or direct assessment during screening visits | Up to 10 years After H. pylori eradication | 
| Mortality from gastric cancer | Cancer registry or other reports | Up to 10 years after eradication | 
| All-cause mortality | Korean National Health Insurance records or other reports | Up to 10 years After H. pylori eradication | 
| Modification of atrophy score | Change in histologic atrophy grade from enrollment to subsequent endoscopic assessment | Up to 10 years After H. pylori eradication | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Helicobacter pylori treatment, Gastric cancer, Screening