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

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

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.

Study Overview

• Status: Unknown
• Conditions: Coronary Artery Disease; Gastroesophageal Reflux Disease
• Intervention / Treatment: Drug: Indobufen and aspirin mimetic; Drug: Aspirin and indobufen mimetic

• Study Type: Interventional
• Enrollment (Anticipated): 88
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100029
    • Beijing Anzhen Hospital, Capital Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Time Frame
AA-induced platelet inhibition rate (LTA method)	2 weeks±4 days
ADP-induced platelet inhibition rate (LTA method)	2 weeks±4 days
Rate of major adverse cardiovascular event (MACE, including all-cause death, non-fatal myocardial infarction, ischemic stroke, ischemia-driven revascularization, or rehospitalization for heart failure)	2 weeks±4 days, 12 weeks±7days
Rate of single endpoint of cardiovascular events, including cardiovascular death, non-fatal myocardial infarction, ischemic stroke, ischemic-driven revascularization, rehospitalization for heart failure, and all-cause death	2 weeks±4 days, 12 weeks±7days

Collaborators and Investigators

• Sponsor: Beijing Anzhen Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): October 17, 2019
• Primary Completion (Anticipated): September 30, 2020
• Study Completion (Anticipated): December 31, 2020

Study Registration Dates

• First Submitted: October 8, 2019
• First Submitted That Met QC Criteria: October 14, 2019
• First Posted (Actual): October 16, 2019

Study Record Updates

• Last Update Posted (Actual): October 16, 2019
• Last Update Submitted That Met QC Criteria: October 14, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: gastroesophageal reflux disease; aspirin; coronary heart disease; indobufen
• Additional Relevant MeSH Terms: Digestive System Diseases; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Gastrointestinal Diseases; Stomach Diseases; Gastroenteritis; Intestinal Diseases; Coronary Disease; Esophageal Motility Disorders; Deglutition Disorders; Esophageal Diseases; Esophagitis; Peptic Ulcer; Duodenal Diseases; Coronary Artery Disease; Gastroesophageal Reflux; Esophagitis, Peptic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Aspirin; Indobufen
• Other Study ID Numbers: 2019026

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No