A large-scale, phase III clinical trial is currently underway in Ardabil, Iran, to determine if long-term, low-dose aspirin can effectively prevent gastric cancer in a high-risk population. The Ardabil Gastric Cancer Prevention Trial (AGCPT) is a population-based, double-blind, placebo-controlled study designed to enroll 21,000 participants between the ages of 35 and 70.
Study Design and Population
Ardabil, a province in northwestern Iran, was selected due to its high incidence of gastric cancer and a significant prevalence of Helicobacter pylori (H. pylori) infection, a known risk factor for the disease. Participants must have resided in Ardabil for at least 10 years and be willing to undergo the study procedures, including providing biological specimens. Exclusion criteria include pregnancy, a history of peptic ulcer disease or gastrointestinal bleeding, severe dyspepsia, prior gastric or esophageal malignancy, known allergy to aspirin, and medical conditions that preclude antibiotic therapy for H. pylori-positive individuals.
Interventions and Outcomes
Eligible participants are first tested for H. pylori. Those testing positive receive standard antibiotic treatment to eradicate the infection. All participants, regardless of their initial H. pylori status (negative at the beginning or after eradication), are then randomized to receive either 81 mg of enteric-coated aspirin or a placebo daily for 10 years. The primary outcome is the difference in the cumulative incidence rate of gastric cancer between the two groups, assessed 5 years after the end of the intervention.
Secondary outcomes include the incidence rate of precancerous gastric lesions (intestinal metaplasia and atrophic gastritis), adverse events (medical events, hospitalizations, all-cause mortality), side effects related to the study drugs, and risk or protective factors associated with gastric cancer.
Data Collection and Monitoring
Data collection involves comprehensive assessments of general, physiological, lifestyle, medical, nutritional, and environmental factors. Biological samples, including blood, stool, urine, hair, and nail samples, are collected and stored in a biobank. Participants are followed up annually for 10 years to monitor adherence, outcomes, complications, and adverse events. Adherence is assessed through self-report questionnaires, pill counts, and measurement of aspirin ingredients in blood and urine samples in a subset of participants.
The trial is monitored by an independent Data Safety and Monitoring Board (DSMB), which has access to all participant data and receives regular reports on response information, adverse events, and audit results. An interim analysis of the primary endpoint will be conducted after 5 years of follow-up to assess the efficacy of aspirin and identify any safety concerns.
Statistical Analysis
The primary analysis will be based on an intention-to-treat principle, comparing the incidence proportion of gastric cancer between the aspirin and placebo groups. Secondary analyses will include case-control comparisons to investigate risk factors for gastric cancer. Statistical methods include chi-squared tests, T-tests, and multivariable logistic regression models. A p-value below 0.05 will be considered statistically significant.
Ethical Considerations
The study protocol has been approved by the Ardabil University of Medical Sciences Ethics Committee and registered in the Iranian Registry of Clinical Trials. All participants provide written informed consent after receiving detailed information about the trial. Data confidentiality is maintained through de-identification and secure data storage.
