Coated or Chewable Aspirin in Patients with Established Atherosclerotic Disease and a Hybrid Strategy to Mitigate the Adverse Effects of Air Pollution: the COATED-AIR Randomized Clinical Trial
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 3,000
- 试验地点
- 1
- 主要终点
- Composite of non-fatal ischemic stroke (not deemed to be related to systolic hypotension), type I myocardial infarction, acute limb events, or cardiovascular death
研究概览
简要总结
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.
详细描述
- Background: Aspirin is a key treatment option of patients with atherosclerotic cardiovascular disease (ASCVD). The enteric coating has emerged as a potential solution to minimize the exposure of the gastric mucosa to the medication. However, change in the medication main site of absorption might negatively impact the pharmacokinetics/pharmacodynamics of aspirin and alter its antithrombotic properties, leading to diminished efficacy of the medication. A sufficiently large randomized controlled trial with a long-term follow-up to compare the effectiveness of enteric-coated versus plain aspirin in reducing adverse cardiovascular events and mitigating the adverse effects of the medication in patients with ASCVD is lacking.
Ambient air pollution is a prominent cause of mortality, being associated with 6.7 million deaths worldwide every year, half of which are attributable to cardiovascular causes. Near the half of these deaths is attributable to cardiovascular causes. Several patient-level interventions have been proposed to counteract with the adverse effects of the air pollution, including alerting patients via text message, staying at home, using face masks, or consuming citrus fruits (as a source of vitamin C) during the days with air pollution. However, the effect of implementing these strategies, individually and especially as a group, in mitigating the adverse effects of the air pollution has not yet been studied in a randomized controlled trial powered for clinical outcomes.
The purpose of the current randomized clinical trial is to compare the efficacy and safety of enteric-coated versus plain low-dose (81 mg) aspirin formulations in a double-blind fashion, and an open-label comparison of a multifaceted intervention including a one-page informational flashcard, cell phone message alerting on days with poor air quality to encourage patients not to spend time outdoors or to wear KN-95 facemasks outdoors in those days, and encouraging patients to consume citrus fruits on highly polluted days (hereafter referred to as hybrid strategy), versus usual care, in a multicenter randomized controlled trial (RCT) with a 2x2 factorial design.
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Design and Randomization method: Multicenter randomized controlled trial with a 2x2 full factorial design with double-blind randomization with a 1:1 allocation ratio to low-dose enteric-coated vs plain aspirin, and open-label randomization with 1:1 allocation ratio to hybrid strategy to reduce the cardiovascular effects of air pollution vs usual care. Permuted block randomization with block sizes of 8, 12 and 16 chosen randomly via an electronic web-based system will be used for the study. The allocation sequence will be concealed. All outcomes will be adjudicated by a Clinical Events Committee blinded to the assigned treatments.
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Setting: Teaching hospitals in Tehran province, Iran will be involved.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
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
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •Willing to participate and able to provide written informed consent
排除标准
- •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)
- •The full list of exclusion criteria is provided in the study protocol
研究组 & 干预措施
Enteric-coated aspirin (+/- hybrid strategy)
81 mg enteric-coated aspirin (+/- a hybrid strategy to mitigate the cardiovascular adverse effects of the air pollution)
干预措施: Enteric-coated aspirin (Drug)
Plain aspirin (+/- hybrid strategy)
81 mg plain aspirin (+/- a hybrid strategy to mitigate the cardiovascular adverse effects of the air pollution)
干预措施: Plain aspirin (Drug)
Hybrid strategy (with enteric-coated or plain aspirin)
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.
干预措施: Hybrid strategy (Other)
结局指标
主要结局
Composite of non-fatal ischemic stroke (not deemed to be related to systolic hypotension), type I myocardial infarction, acute limb events, or cardiovascular death
时间窗: within maximum of 30-month follow-up
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.
Composite of fatal or nonfatal ischemic stroke (not deemed to be related to systemic hypotension), type I myocardial infarction, and acute limb events
时间窗: within maximum of 30-month follow-up
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.
次要结局
- 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)
- Any Major bleeding(within maximum of 30-month follow-up)
- Intracranial hemorrhage(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(within maximum of 30-month follow-up)
- Any clinically relevant non-major bleeding(within maximum of 30-month follow-up)
- New symptomatic diagnosed gastroduodenal ulcer(within maximum of 30-month follow-up)
- Type I myocardial infarction(within maximum of 30-month follow-up)
- Unplanned vascular hospitalization(within maximum of 30-month follow-up)
- Upper GI bleeding(within maximum of 30-month follow-up)
- Clinically relevant non-major GI bleeding(within maximum of 30-month follow-up)
研究者
Parham Sadeghipour
Dr.
Rajaie Cardiovascular Medical and Research Center