Coated or Chewable Aspirin and a Hybrid Strategy to Mitigate Adverse Effects of Air Pollution in Stable Atherosclerotic Disease

NCT06541691 | Recruiting DMC

• 1 other identifier: 4020310
• Study Type: interventional
• Target: 3,000
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Atherosclerotic Cardiovascular Disease; Coronary Artery Disease; Ischemic Heart Disease; Ischemic Stroke; Peripheral Arterial Disease; Carotid Artery Stenosis; Carotid Atherosclerosis

Keywords

atherosclerosis; atherosclerotic cardiovascular disease; atherosclerotic arterial disease; atherosclerotic plaque; coronay artery disease; ischemic heart disease; atherosclerotic disease; ischemic stroke; peripheral arterial disease; carotid artery stenosis; carotid atherosclerosis; myocardial infarction; acute limb ischemia; bleeding; major bleeding; gastrointestinal bleeding; gastrointestinal ulcer; peptic ulcer disease; gastric ulcer; duodenal ulcer; dyspepsia; intracerebral hemorrhage; aspirin; acetylsalicylic acid; antithrombotic therapy; antithrombotic agents; antiplatelet agents; air pollution; cerebral hemorrhage; hemorrhage

Outcome Measures

Primary Outcomes (2)

• Composite of fatal or nonfatal ischemic stroke (not deemed to be related to systemic hypotension), type I myocardial infarction, and acute limb events

  Time to the first occurrence of an outcome composed of any endpoint that fulfills the definite criteria for diagnosis of at least one of the ischemic stroke, type I myocardial infarction, or acute limb event (whether leading to the patient's death or not) as defined in the description of the related secondary outcomes 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

  Time to the first occurrence of an outcome composed of any endpoint that fulfills the definite criteria for diagnosis of at least one of the ischemic stroke, type I myocardial infarction, or acute limb event, and don not result in patient death as defined in the description of the related secondary outcomes This outcome is assigned as the primary outcome for the second randomization.

  within maximum of 30-month follow-up

Secondary Outcomes (13)

• Type I myocardial infarction

  within maximum of 30-month follow-up

• Ischemic stroke (not deemed to be related to systemic hypotension)

  within maximum of 30-month follow-up

• Acute limb event

  within maximum of 30-month follow-up

• All-cause death

  within maximum of 30-month follow-up

• Cardiovascular death

  within maximum of 30-month follow-up

Study Arms (4)

Enteric-coated aspirin (+/- hybrid strategy)

EXPERIMENTAL

81 mg enteric-coated aspirin (+/- a hybrid strategy to mitigate the cardiovascular adverse effects of the air pollution)

Drug: Enteric-coated aspirin

Plain aspirin (+/- hybrid strategy)

ACTIVE COMPARATOR

81 mg plain aspirin (+/- a hybrid strategy to mitigate the cardiovascular adverse effects of the air pollution)

Drug: Plain aspirin

Hybrid strategy (with enteric-coated or plain aspirin)

EXPERIMENTAL

A hybrid strategy to mitigate the cardiovascular adverse effects the air pollution, composed of 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.

Other: Hybrid strategy

Usual care (with enteric-coated or plain aspirin)

NO INTERVENTION

No active strategy (usual care) without any clear recommendations related to air pollution; only a control card will be shared with the patients randomized to the usual care

Interventions

Enteric-coated aspirin DRUG

Enteric-coated aspirin tablet 81 mg, once daily

Also known as: Low dose of enteric-coated aspirin

Enteric-coated aspirin (+/- hybrid strategy)

Plain aspirin DRUG

Plain aspirin tablet 81 mg, once daily

Also known as: Low dose of plain aspirin

Plain aspirin (+/- hybrid strategy)

Hybrid strategy OTHER

A hybrid strategy composed from: * A one-page educational flashcard * Alerting patients on highly polluted days via text message * Encouraging patients to stay at home or minimizing outdoor activity on highly polluted days * Encouraging patients via text message to wear KN-95 facemasks (provided by the investigators of this study) during outdoors time on highly polluted days * Encouraging patients to consume citrus fruits during highly polluted days

Also known as: The hybrid strategy to mitigated the cardiovascular adverse effects of the air pollution

Hybrid strategy (with enteric-coated or plain aspirin)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients (≥18 years) with documented ASCVD defined as at least one of the following:
• Coronary artery disease (CAD):
• Previous or recent documented type I myocardial infarction \*(if not specified, will be assumed as type I)
• History of coronary revascularization (percutaneous coronary intervention or coronary artery bypass graft surgery)
• History of obstructive CAD (\>50% stenosis) documented by coronary computed tomography (CT) or conventional angiography
• Peripheral arterial disease (PAD):
• Previous or recent acute ischemic limb event (\>7 days prior)
• History of previous endovascular/surgical lower or upper extremities revascularization for an atherosclerotic cause
• History of ulcer or lower extremities amputation due to ASCVD.
• Carotid arterial diseases:
• History of previous endovascular/surgical carotid artery revascularization for atherosclerotic causes
• History of \> 50% carotid artery stenosis based on documented imaging tests (Duplex US, CT angiography, magnetic resonance angiography, or conventional angiography)
• Ischemic stroke:
• History of recent or previous documented ischemic stroke not due to atrial fibrillation, endocarditis, or systemic hypoperfusion/hypotension, being treated with low-dose aspirin
• Inhabitant of Tehran province

You may not qualify if:

• Being within 72 days of acute/unstable atherosclerotic cardiovascular events (acute myocardial infarction, acute limb event, and acute ischemic stroke), or within 72 hours of revascularization.
• Patients receiving triple antithrombotic therapy
• History of upper gastrointestinal bleeding within the past 30 days
• History of intracranial hemorrhage within the past 30 days
• End-stage kidney disease with estimated creatinine clearance \< 15 mL/min, or undergoing hemodialysis or peritoneal dialysis
• Known comorbidities associated with poor prognosis (e.g., metastatic cancer) in conjunction with an estimated life expectancy of less than one year according to the treating clinician
• Any other conditions that make the participants unsuitable for recruitment or follow-up (e.g., illiteracy)
• Not having aspirin as part of the planned durable treatment regimen
• Inability to receive/read text messages/phone calls by personal mobile phone (or that of a caregiver who lives with the patient and is willing to relay messages)

Sponsors & Collaborators

• Rajaie Cardiovascular Medical and Research Center: lead
• Brigham and Women's Hospital: collaborator

Study Sites (1)

Rajaie Cardiovascular Medical and Research Center

Tehran, Tehran Province, 1995614331, Iran

RECRUITING

MeSH Terms

Conditions

Atherosclerosis; Coronary Artery Disease; Myocardial Ischemia; Ischemic Stroke; Peripheral Arterial Disease; Carotid Stenosis; Carotid Artery Diseases; Plaque, Atherosclerotic; Myocardial Infarction; Hemorrhage; Gastrointestinal Hemorrhage; Peptic Ulcer; Stomach Ulcer; Duodenal Ulcer; Dyspepsia; Cerebral Hemorrhage

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Coronary Disease; Heart Diseases; Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Peripheral Vascular Diseases; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Infarction; Ischemia; Pathologic Processes; Necrosis; Gastrointestinal Diseases; Digestive System Diseases; Duodenal Diseases; Intestinal Diseases; Stomach Diseases; Signs and Symptoms, Digestive; Signs and Symptoms; Intracranial Hemorrhages

Study Officials

• Parham Sadeghipour, M.D

  Rajaie Cardiovascular Medical and Research Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Parham Sadeghipour, MD

CONTACT

+982123921; psadeghipour@hotmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The quadruple masking (Participant, Treating Clinician, Investigator, Outcomes Assessor) is used for the first randomization, and the second randomization is open-label with blinded adjudication
• Purpose: PREVENTION
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr.

Model Details: 2×2 full factorial design

Study Record Dates

• First Submitted: August 2, 2024
• First Posted: August 7, 2024
• Study Start: March 6, 2024
• Primary Completion: March 30, 2026
• Study Completion (Estimated): March 30, 2027
• Last Updated: March 19, 2025

Record last verified: 2024-08

Locations

IR (1)