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

Official title

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

Overview

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

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.

Interventions

• Drug Aspirin 100mg
  Daily aspirin 100 mg for 5 years
• Drug Placebo oral tablet
  Daily placebo for 5 years

Primary outcome measures

• The incidence of gastric cancer between the intervention and placebo groups [Time frame: Until last enrolled patients take 5-year trial medication]

Secondary outcome measures (6)

• All-cause mortality [Time frame: Until last enrolled patients take 5-year trial medication]
• The incidence of cardiovascular disease and cerebrovascular disease between the intervention and placebo groups [Time frame: Until last enrolled patients take 5-year trial medication]
• The incidence of other organ cancers between the intervention and placebo groups [Time frame: Until last enrolled patients take 5-year trial medication]
• The incidence of gastric dysplasia (adenoma) between the intervention and placebo groups [Time frame: Until last enrolled patients take 5-year trial medication]
• Complication related to the aspirin use [Time frame: Until last enrolled patients take 5-year trial medication]
• Improvement of atrophy and intestinal metaplasia [Time frame: At the time of 5-year trial medication]

Eligibility criteria

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%

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Prevention

Study locations

South Korea · 10 centers

• Pusan National University Hospital — Busan
• Kosin University Gospel Hospital — Busan
• Hallym University Chuncheon Sacred Heart Hospital — Chuncheon
• Kyungpook National University Chilgok Hospital — Daegu
• National Cancer Center — Goyang
• Chonnam National University Hospital — Gwangju
• Incheon St.Mary's Hospital/The Catholic University — Incheon
• Chung-Ang University Hospital — Seoul
• … and 2 more centers

Identifiers

NCT: NCT04214990 · NCC2019-0184

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗