Aspirin Use for Gastric Cancer Prevention in the Early Gastric Cancer Patients

Study Overview
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Brief Summary
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This study aimed to investigate the effect of low-dose (100 mg) asprin on the prevention of gastric cancer in the early gastric cancer patients with negative H. pylori status who underwent endoscopic submucosal dissection.

Detailed Description
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Aspirin has been widely used as an anti-platelet drug for the primary or secondary prevention of cardiovascular events, including ischemic heart disease and stroke. In 2016, the U.S. Preventive Services Task Force recommended initiating low-dose aspirin use for the primary prevention of cardiovascular diseases and colorectal cancer in adult aged 50 to 59 years who have a 10% or greater 10-year cardiovascular disease risk, are not at increased risk of bleeding, have a life expectancy of at least 10 years, and are willing to take low-dose aspirin daily for at least 10 years. In addition, a meta-analysis reported that long-term aspirin use was associated with reduced the risk of gastrointestinal cancers including colorectal cancer, esophageal cancer, and gastric cancer. However, most studies that reported the cancer prevention effect of long-term aspirin use were conducted as a secondary analysis or subgroup analysis of primary studies investigating the aspirin use for cardiovascular disease prevention. Thus, there is a limitation that appropriate sample sizes and follow-up periods for the cancer prevention effect of aspirin were not considered. In 2018, we reported that H. pylori treatment reduced the development of metachronous gastric cancer after endoscopic resection in early gastric cancer patients. However, metachronous gastric cancer could develop after successful H. pylori eradication with an annual incidence of 1%-3%. Therefore, we designed a multi-center, double-blind, randomized, placebo-controlled trial to evaluate whether long-term low-dose (100 mg) aspirin uses prevents gastric cancer in early gastric cancer or high-grade dysplasia patients who underwent endoscopic resection.

Official Title
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Effect of Low-dose Aspirin for Stomach Cancer Prevention After Endoscopic Resection of Gastric Neoplasm (EASTERN): a Randomized Controlled Trial

Conditions
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Aspirin, Gastric Cancer

Intervention / Treatment
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* Drug: Aspirin 100mg
* Drug: Placebo oral tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women aged 19-70 years who underwent endoscopic resection for high-grade adenoma or early gastric cancer (category 4 [non-invasive high grade neoplasm] or category 5 [invasive neoplasia] according to the Vienna classification of gastrointestinal epithelial neoplasia [Schlemper RJ, et al. Gut 2000;47:251-255.]) Final pathological results after endoscopic resection met the absolute or expanded criteria according to the Japanese Gastric Cancer Treatment guideline 2014 (version 4) Patients who had negative H. pylori status or those who eradicated H. pylori status Willingness to sign an informed consent form Exclusion Criteria: Patients who received aspirin for the secondary prevention of cardiovascular diseases or cerebrovascular diseases Regular aspirin uses (more than 3 times a week) with 2 months before screening visit Patients who used anticoagulants or antiplatelet drugs for therapeutic purpose Previous gastrectomy history Current treatment for serious medical condition which could hinder participation (such as severe heart dysfunction, liver cirrhosis, renal failure, COPD or bronchial asthma, or uncontrolled infection) High risk patients for bleeding complications (cerebral aneurysm, vascular malformation, esophageal or gastric varices, or hemophilia, etc) Active peptic ulcer disease (patients who treated peptic ulcer completely could be enrolled) Diagnosis and active treatment for other organ cancer (except carcinoma in situ, and non-melanoma skin cancer) within 5 years Non-curative resection of early gastric cancer after endoscopic resection Aspirin allergy or contraindication of aspirin use Pregnant or lactating women Alcoholism, drug abuse Inadequate patients for study enrollment according to the evaluation of the study physician Inability to provide an informed consent Patients who took a 28-day run-in-period medication less than 80%

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 70 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: Aspirin<br>Enteric coated aspirin | Drug: Aspirin 100mg<br>* Daily aspirin 100 mg for 5 years<br>|
| Placebo Comparator: Placebo<br>Enteric coated aspirin placebo | Drug: Placebo oral tablet<br>* Daily placebo for 5 years<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 cancer detected at follow-up endoscopy or registered at the Korean Cancer Registry | Until last enrolled patients take 5-year trial medication | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause mortality | Mortality from any causes | Until last enrolled patients take 5-year trial medication | 
| The incidence of cardiovascular disease and cerebrovascular disease between the intervention and placebo groups | Cardiovascular diseases (stable and unstable angina, myocardial infarction); Cerebrovascular diseases (transient ischemic attack, cerebral infarction, other small vascular infarction, etc) | Until last enrolled patients take 5-year trial medication | 
| The incidence of other organ cancers between the intervention and placebo groups | Cancers detected at follow-up visits or registered at the Korean Cancer Registry | Until last enrolled patients take 5-year trial medication | 
| The incidence of gastric dysplasia (adenoma) between the intervention and placebo groups | Histologically confirmed gastric dysplasia (adenoma) detected at follow-up endoscopy | Until last enrolled patients take 5-year trial medication | 
| Complication related to the aspirin use | Gastrointestinal bleeding, intracranial hemorrhage, subarachnoid hemorrhage, and other bleeding complications | Until last enrolled patients take 5-year trial medication | 
| Improvement of atrophy and intestinal metaplasia | Change in histologic atrophy and intestinal metaplasia grades from enrollment to subsequent endoscopic assessment | At the time of 5-year trial medication | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Aspirin, Gastric cancer prevention, Endoscopic submucosal dissection