GaStroEsophageal effeCt of indobUfen Versus aspiRin in Patients Undergoing Dual antiplatElet Therapy

Study Overview
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Brief Summary
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The dual antiplatelet therapy based on aspirin plays an important role in the treatment of patients with coronary heart disease. Although aspirin is widely used and effective, it has many limitations in the long-term including increased risk of bleeding. In patients with coronary heart disease and gastroesophageal reflux disease, the symptoms of gastroesophageal reflux are usually aggravated after the application of aspirin. As an antiplatelet drug, indobufen can reversibly and selectively inhibit platelet cyclooxygenase-1 (COX-1), thereby blocking the synthesis of thromboxane B2 (TXB2) and exerting its antiplatelet effect, and it does not affect the production of prostaglandins and endothelial prostacyclins in gastrointestinal mucosa. It has less gastrointestinal injury and lower risk of bleeding. This project is to study the effects of indobufen or aspirin on gastric acid secretion and gastroesophageal reflux in patients with coronary heart disease and gastroesophageal reflux disease treated with dual antiplatelet therapy.

Official Title
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Effect of Indobufen Versus Aspirin on Gastric Acid Secretion and Gastroesophageal Reflux in Patients With Coronary Heart Disease and Gastroesophageal Reflux Disease Undergoing Dual Antiplatelet Therapy: a Prospective, Randomized, Double-blind, Double-dummy, Positive Drug Parallel Control Clinical Trials

Conditions
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Coronary Artery Disease, Gastroesophageal Reflux Disease

Intervention / Treatment
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* Drug: Indobufen and aspirin mimetic
* Drug: Aspirin and indobufen mimetic


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-75 years Patients with stable and unstable angina pectoris receiving dual antiplatelet therapy (combined with clopidogrel) Coronary angiography indicating ≥50% stenosis in >2.0 mm vessels Gastroesophageal Reflux Disease Diagnostic Questionnaire Score (≥8) Signed informed consent Exclusion Criteria: Acute myocardial infarction within 1 month before admission Patients undergoing treatment related to gastroesophageal reflux disease (e.g. proton pump inhibitors, etc.) Patients receiving other antiplatelet drugs (such as cilostazol) and oral anticoagulants Patients with cardiogenic shock (systolic blood pressure <90 mmHg and/or diastolic blood pressure <60 mmHg), severe heart failure (killip grade ≥3), hepatic insufficiency (AST/ALT more than twice the upper limit of normal value caused by non-cardiac diseases), prior stroke and renal dysfunction (GFR <60 ml/min) Those with active hemorrhage, hemorrhagic diseases or tendency to bleeding, especially those with a history of cerebral hemorrhage People who are known to be intolerant or allergic to aspirin, indobufen or clopidogrel Patients with malignant tumors or with life expectancy <2 years Pregnant women, lactating women, women of childbearing age who do not take effective contraceptive measures, or those who plan to conceive during the trial, or those who have positive results of HCG examination before the trial Those who have participated in other clinical trials or are currently participating in other clinical trials within one month before the trial According to the judgement of the researchers, patients could not complete the study or comply with the requirements of the study (e.g. memory or behavioral disorders, mental disorders, alcohol dependence, prior defaults)

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Indobufen<br> | Drug: Indobufen and aspirin mimetic<br>* Day 1 to 84±7: The first time: indobufen 100mg + aspirin mimetic; The second time: indobufen 100mg<br>|
| Active Comparator: Aspirin<br> | Drug: Aspirin and indobufen mimetic<br>* Day 1 to 84±7: The first time : aspirin 100mg+ indobufen mimetic; The second time: indobufen mimetic<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage time of intragastric pH<4.0 during 24-hour intragastric pH monitoring | This parameter will be detected by 24-hour intragastric pH monitoring (Medical Measurement Systems, Netherlands) | 2 weeks±4 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median value of intragastric pH during 24-hour intragastric pH monitoring | This parameter will be detected by 24-hour intragastric pH monitoring (Medical Measurement Systems, Netherlands) | 2 weeks±4 days | 
| Frequency of indigestion occurrence |  | 2 weeks ±4 days, 12 weeks±7 days | 
| Rate of bleeding events (BARC criteria) |  | 2 weeks ±4 days, 12 weeks±7 days | 
| Gastroesophageal reflux disease questionnaire score (GerdQ score) | Min 0, max 18, and higher scores mean a worse outcome | 2 weeks ±4 days, 12 weeks±7 days | 
| AA-induced platelet inhibition rate (TEG method) |  | 2 weeks ±4 days | 
| ADP-induced platelet inhibition rate (TEG method) |  | 2 weeks ±4 days | 
| DeMeester score | Min 0, no upper limit, and higher scores mean a worse outcome | 2 weeks ±4 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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aspirin, coronary heart disease, gastroesophageal reflux disease, indobufen