Coated or Chewable Aspirin and a Hybrid Strategy to Mitigate Adverse Effects of Air Pollution in Stable Atherosclerotic Disease
NCT Number: NCT06541691
Acronym: COATED-AIR
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: NA
Conditions: Atherosclerotic Cardiovascular Disease|Coronary Artery Disease|Ischemic Heart Disease|Ischemic Stroke|Peripheral Arterial Disease|Carotid Artery Stenosis|Carotid Atherosclerosis
Interventions: DRUG: Enteric-coated aspirin|DRUG: Plain aspirin|OTHER: Hybrid strategy
Sponsor: Rajaie Cardiovascular Medical and Research Center
Collaborators: Brigham and Women's Hospital
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 3000
Study Design: Allocation: RANDOMIZED|Intervention Model: FACTORIAL|Masking: QUADRUPLE (PARTICIPANT, CARE_PROVIDER, INVESTIGATOR, OUTCOMES_ASSESSOR)|Primary Purpose: PREVENTION
Start Date: 2024-03-06
Completion Date: 2027-03-30
Locations: Rajaie Cardiovascular Medical and Research Center, Tehran, 1995614331, Iran, Islamic Republic of

Summary:
Although both enteric-coated and plain formulations of aspirin are being used commonly, there are no high-quality comparisons between these formulations with respect to clinical efficacy outcomes in patients with atherosclerotic cardiovascular diseases (ASCVD). Air pollution is also a major contributor to the excess risk of cardiovascular events in many regions of the world. However, little is known about the effect of individual-level mitigation strategies against air pollution in reducing cardiovascular outcomes. The purpose of the first randomization is to compare the efficacy and safety of enteric-coated versus plain low-dose (81 mg) aspirin formulations in a double-blind fashion. The second randomization compares a multifaceted intervention including one-page educational flashcard, cell phone text messages alerting participants on polluted days, recommending them to stay indoors or wear KN-95 facemasks provided by the study team in case of necessary outdoor activity, and recommendation to consume citrus fruits on polluted days versus usual care. Both randomization are powered for clinical outcomes and the results will inform practice.

Primary Outcome Measures: Composite of fatal or nonfatal ischemic stroke (not deemed to be related to systemic hypotension), type I myocardial infarction, and acute limb events, This outcome is assigned as the primary efficacy outcome for the first randomization., within maximum of 30-month follow-up|Composite of non-fatal ischemic stroke (not deemed to be related to systolic hypotension), type I myocardial infarction, acute limb events, or cardiovascular death, This outcome is assigned as the primary outcome for the second randomization., within maximum of 30-month follow-up
Secondary Outcome Measures: Type I myocardial infarction, Spontaneous clinical syndrome related to atherosclerotic plaque rupture, ulceration, fissuring, erosion, or dissection, with resulting intraluminal thrombus and leading to decreased myocardial blood flow or distal platelet emboli with ensuing myocyte necrosis. This classification requires the detection of a rise and/or fall of cardiac biomarker values (preferably cTn) with at least 1 value \>99th percentile of the URL and at least 1 of the following: 1- Symptoms of myocardial ischemia 2- New or presumed new significant ST-segment T wave changes or new left bundle branch block on the ECG 3- Development of pathological Q waves on the ECG 4- Imaging evidence of new loss of myocardium or new regional wall motion abnormality 5- Identification of an intracoronary thrombus by angiography or autopsy, within maximum of 30-month follow-up|Ischemic stroke (not deemed to be related to systemic hypotension), An episode of acute neurological dysfunction caused by focal cerebral, spinal, or retinal infarction as a result of arterial thrombosis and/or thromboembolism (not deemed to be related to systemic hypotension/hypoperfusion), and lasting ≥ 24 hours or to time of death with residual neurological sequelae, within maximum of 30-month follow-up|Acute limb event, A limb-threatening ischemia that is confirmed by limb hemodynamics or imaging and leads to an acute vascular intervention (i.e., pharmacologic \[heparin, thrombolysis\], peripheral arterial surgery/reconstruction, peripheral angioplasty/stenting, and/or limb amputation) within 30 days of onset of symptoms. In case of lack of confirmation by limb hemodynamics or imaging, the absence of pedal pulses is acceptable as the hemodynamic criterion for acute limb ischemia, within maximum of 30-month follow-up|All-cause death, Death due to any causes (cardiovascular, non-cardiovascular, or undetermined) within the follow-up period, within maximum of 30-month follow-up|Cardiovascular death, Cardiovascular death is defined as death resulting from cardiovascular causes. The following categories may be collected: 1- Death caused by acute MI 2- Death caused by sudden cardiac, including unwitnessed, death 3- Death resulting from heart failure 4- Death caused by stroke 5- Death resulting from cerebrovascular hemorrhage 6- Death resulting from other cardiovascular causes such as PE, acute aortic syndromes, arrhythmia, and others, within maximum of 30-month follow-up|Unplanned vascular hospitalization, Inpatient admission to a hospital specifically due to acute events involving the vascular system. This encompasses conditions such as acute myocardial infarction, ischemic or hemorrhagic stroke, acute limb ischemia, and other vascular emergencies necessitating urgent medical care and hospitalization, within maximum of 30-month follow-up|Composite of International Society on Thrombosis and Haemostasis (ISTH) major or clinically-relevant non-major gastrointestinal (GI) bleeding that bleeding and new symptomatic diagnosed gastroduodenal ulcer, An outcome composed of any GI bleeding that fulfills the ISTH criteria for major or clinically-relevant non-major bleeding (defined in the description of the related secondary outcomes), and/or any newly diagnosed symptomatic gastroduodenal ulcer that meets the definition described in the description of the related secondary outcomes.

This outcome is considered as the primary safety outcome for the first randomization., within maximum of 30-month follow-up|Upper GI bleeding, Bleeding originating from sites in the esophagus, stomach, or duodenum with manifestations including hematemesis (vomiting of red blood or coffee-grounds material), melena (black, tarry stool), or hematochezia (passage of red or maroon material per rectum). Major and clinically relevant non-major UGIB will also be discriminated., within maximum of 30-month follow-up|Clinically relevant non-major GI bleeding, Bleeding from the upper or lower gastrointestinal tract that meets the criteria for the ISTH definition for clinically-relevant non-major bleeding (Please see below for these two definitions)., within maximum of 30-month follow-up|Any Major bleeding, Any bleeding event fulfills the ISTH major bleeding criteria in non-surgical patients defined as having a symptomatic presentation and: 1- Fatal bleeding and/or 2- Bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intra-articular or pericardial, or intramuscular with compartment syndrome and/or 3- Bleeding causing a fall in hemoglobin level of 20 g/L (1.24 mmol/L) or more, or leading to transfusion of two or more units of whole blood or red cells., within maximum of 30-month follow-up|Intracranial hemorrhage, The abnormal bleeding within the confines of the skull, involving either the brain tissue (intracerebral hemorrhage) or the spaces between the layers that cover the brain (subarachnoid or subdural hemorrhage)., within maximum of 30-month follow-up|Any clinically relevant non-major bleeding, Any sign or symptom of hemorrhage (e.g., more bleeding than would be expected for a clinical circumstance, including bleeding found by imaging alone) that does not fit the criteria for the ISTH definition of major bleeding but does meet at least one of the following criteria: 1- Requiring medical intervention by a healthcare professional 2- Leading to hospitalization or increased level of care 3- Prompting a face-to-face (i.e., not just a telephone or electronic communication) evaluation., within maximum of 30-month follow-up|New symptomatic diagnosed gastroduodenal ulcer, Gastroduodenal ulcer manifested by gastrointestinal symptoms that persist for \> 3 days, with confirmation of ulcer by endoscopy. An ulcer is defined as any mucosal break at least 3 mm in greatest diameter, within maximum of 30-month follow-up