Effects of H. Pylori Eradication on the Gastric Preneoplastic Lesion and Neoplasm After ESD

Study Overview
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Brief Summary
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This study evaluates whether Helicobacter pylori eradication improves precancerous lesions including glandular atrophy and intestinal metaplasia as well as metachronous cancers or dysplasias after endoscopic mucosal resection for gastric cancer.

Detailed Description
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Helicobacter pylori is a primary etiological agent leading to chronic gastritis and peptic ulcer. The organism is also associated with gastric cancer in epidemiological studies. However detailed mechanism of carcinogenesis remains unknown. Histolopathological studies indicate that chronic H. pylori infection progresses over decades through stages of chronic gastritis, atrophy, intestinal metaplasia, dysplasia and cancer. Gastric atrophy and intestinal metaplasia are considered as precancerous lesions, but whether H. pylori eradication improves these lesions and prevents metachronous gastric cancer is controversial. And the issue has not been evaluated in gastric cancer patients. However, despite the conflicting evidences from two open labelled randomized controlled trials, current guidelines from various regions recommend H. pylori eradication treatment in patients who were treated for gastric cancer by surgically or endoscopically. Thus, it is important to evaluate whether H. pylori eradication can improve known precancerous lesion, i.e. glandular atrophy and intestinal metaplasia in gastric cancer patients. Such histological improvement can eventually reduce secondary gastric cancer development and provide evidence for current guidelines.

Official Title
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Effect of Helicobacter Pylori Eradication on Glandular Atrophy and Metachronous Cancer in Patients Undergoing Endoscopic Mucosal Resection for Gastric Cancer

Conditions
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Helicobacter Pylori Infection, Early Gastric Cancer, Endoscopic Resection

Intervention / Treatment
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* Drug: 7 day H.pylori eradication Omeprazole or Rabeprazole, Clarithromycin, Amoxicillin
* Drug: Placebo, Omeprazole or Rabeprazole, Clarithromycin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Early Gastric cancer or high grade dysplasia confirmed by endoscopy Histologically confirmed well or moderately differentiated adenocarcinoma, or high grade dysplasia Submucosal invasion is not suspected No evidence of ulceration or ulcer scar within the lesion Helicobacter pylori infection was confirmed by histological evaluation and rapid urease test Pre op CT stage: IA (T1N0M0) according to UICC TNM classification system Informed consent should be signed Exclusion Criteria: Recurrent gastric cancer Previous serious side effect to antibiotics H. pylori eradication treatment history Poorly differentiated adenocarcinoma or Signet ring cell carcinoma Undergoing operation due to complication of EMR Undergoing operation due to remnant cancer Other malignancy within the past 5 years Pregnant or nursing women Serious concurrent infection or nonmalignant disease such as liver cirrhosis, renal failure, cardiovascular diseases Psychiatric disorder that would preclude compliance

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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: 7 day H.pylori eradication<br>Treatment: Omeprazole 20 mg or Rabeprazole 10 mg bid + clarithromycin 500 mg and amoxicillin 1,000 mg bid for 7 days | Drug: 7 day H.pylori eradication Omeprazole or Rabeprazole, Clarithromycin, Amoxicillin<br>* Omeprazole 20 mg or Rabeprazole 10 mg bid for 7 days, Clarithromycin 500 mg bid for 7 days, Amoxicillin 1,000 mg bid for 7 days.<br>* Other names: 7 day Proton pump inhibitor (PPI)-based standard triple therapy;|
| Placebo Comparator: Placebo<br>Omeprazole 20 mg or Rabeprazole 10 mg bid + Placebo for two antibiotics (clarithromycin and amoxicillin) bid for 7 days | Drug: Placebo, Omeprazole or Rabeprazole, Clarithromycin<br>* Omeprazole 20 mg or Rabeprazole 10 mg bid for 7 days, Placebo for clarithromycin 500 mg bid for 7 days, Placebo for amoxicillin 1,000 mg bid for 7 days.<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement (histological) of glandular atrophy | Improvement of glandular atrophy at the corpus lesser curvature | 3 years after enrollment | 
| Incidence of metachronous gastric cancer | Comparison of metachronous gastric cancer according to the allocated treatment | 3 years after last patient enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of new gastric dysplasia | Comparison of new gastric dysplasia according to the allocated treatment | 3 years after last patient enrollment | 
| Overall survival | Comparison of overall survival according to the allocated treatment | 3 years after last patient enrollment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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H. pylori eradication, Atrophy, Intestinal metaplasia, Endoscopic resection, Stomach neoplasm