NCT04217447终止3 期
Assessment of Quitting Versus Using Aspirin Therapy In Patients Treated With Oral Anticoagulation for Atrial Fibrillation or Other Indication With Stabilized Coronary Artery Disease
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 874
- 试验地点
- 51
- 主要终点
- Primary efficacy outcome : rate of composite of cardiovascular mortality and thrombotic cardiovascular events
研究概览
简要总结
- Long-term aspirin (ASA) is the standard recommended antithrombotic therapy in patients with stable coronary artery disease (CAD), especially following stenting (Class I, Level A).
- Long-term oral anticoagulation (OAC) is the standard antithrombotic therapy in patients with atrial fibrillation (AF) associated with one or more risk factor for stroke (Class I, Level A).
- During the first year following acute coronary syndrome (ACS) and/or percutaneous coronary intervention (PCI), several studies evaluating the combination of OAC treatment and antiplatelet therapy are either already published or ongoing.
- At distance of the index ACS and/or PCI, patients with stable CAD and concomitant AF remain at particular high-risk of ischemic (3 to 4 times higher as compared to patients with stable CAD without AF) and bleeding events. Antithrombotic management of these patients is subsequently highly challenging in clinical practice. The European task force suggests that the use of a full-dose anticoagulant monotherapy without any antiplatelet therapy should be the default strategy in such patients with both, AF and stable CAD.
- However, evidences are sparse and weak to support such a strategy (only observational studies with many biases) and no randomized trial has assessed this question. These patients, especially those at high-risk of recurrent ischemic events (post- ACS, diabetes, multivessel CAD...) may benefit from the combination of OAC and aspirin at long-term. Indeed the crude event rate of ischemic events is much higher than the crude event rate of bleeding in this specific population. Ischemic events are 2 to 3 times more frequent than bleeding in daily practice.
- The benefit/risk ratio of these two different strategies (ASA in combination with OAC vs. OAC alone) in patients at high-risk of recurrent coronary and vascular events remains unknown. Dual therapy with full-dose anticoagulation and ASA may lead to higher risk of major bleeding, while stopping ASA in stabilized high-risk patients after PCI may lead to poorer outcome regarding ischemic events.
- The coordinating investigators therefore designed a double blind placebo controlled trial in order to assess the optimal antithrombotic regimen that should be pursued long-life in this subset of patients.
详细描述
- Long-term aspirin (ASA) is the standard recommended antithrombotic therapy in patients with stable coronary artery disease (CAD), especially following stenting (Class I, Level A).
- Long-term oral anticoagulation (OAC) is the standard antithrombotic therapy in patients with atrial fibrillation (AF) associated with one or more risk factor for stroke (Class I, Level A).
- During the first year following acute coronary syndrome (ACS) and/or percutaneous coronary intervention (PCI), several studies evaluating the combination of OAC treatment and antiplatelet therapy are either already published or ongoing.
- At distance of the index ACS and/or PCI, patients with stable CAD and concomitant AF remain at particular high-risk of ischemic (3 to 4 times higher as compared to patients with stable CAD without AF) and bleeding events. Antithrombotic management of these patients is subsequently highly challenging in clinical practice. The European task force suggests that the use of a full-dose anticoagulant monotherapy without any antiplatelet therapy should be the default strategy in such patients with both, AF and stable CAD.
- However, evidences are sparse and weak to support such a strategy (only observational studies with many biases) and no randomized trial has assessed this question. These patients, especially those at high-risk of recurrent ischemic events (post- ACS, diabetes, multivessel CAD...) may benefit from the combination of OAC and aspirin at long-term. Indeed the crude event rate of ischemic events is much higher than the crude event rate of bleeding in this specific population. Ischemic events are 2 to 3 times more frequent than bleeding in daily practice.
- The benefit/risk ratio of these two different strategies (ASA in combination with OAC vs. OAC alone) in patients at high-risk of recurrent coronary and vascular events remains unknown. Dual therapy with full-dose anticoagulation and ASA may lead to higher risk of major bleeding, while stopping ASA in stabilized high-risk patients after PCI may lead to poorer outcome regarding ischemic events.
AQUATIC is a prospective, randomized, double-blind, placebo controlled, parallel-group, multi-center study.
Randomization into 2 treatment groups and stratified on study center, type of OAC (VKA vs. DOAC), antithrombotic treatment received at the time of inclusion (dual therapy combining single antiplatelet therapy + OAC vs. OAC alone).
Experimental group : Patients intaking full-dose OAC + ASA 100mg od.
Control group : Patients intaking full-dose OAC + Placebo of ASA 100mg od.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Patients >18 year-old
- •All patients that need anticoagulation with direct oral anticoagulant (DOAC) or vitamin K antagonist (VKA) for AF (paroxysmal, persistent or permanent) or other indication and have a stabilized CAD (free from MI, or coronary revascularization in the past year) but remain at high residual risk of recurrent coronary and vascular events. The use of DOAC will be promoted as recommended by guidelines.
- •Two different categories of patients could be included in the study, i) patients treated at the time of inclusion with the association of OAC and single antiplatelet therapy, it will be tested for them aspirin vs. interruption of antiplatelet therapy ii) patients treated with OAC alone at the time of inclusion, it will be tested for them administration of aspirin vs. no additional treatment with aspirin.
- •High-risk of coronary and vascular event is defined as follow :
- •History of PCI during an ACS involving placement of ≥1 stent(s) since >6 months.
- •History of PCI (>6 months) outside the context of ACS but with high-risk features of ischemic event recurrences defined as: diabetes, or diffuse multivessel disease (defined by the involvement of the 3 coronary vessels), or chronic kidney disease (creatinine clearance < 50ml/min), or prior stent thrombosis, or complex PCI (defined by: stenting of the last remaining patent coronary artery, left main, at least 3 stents implanted and/or 3 lesions treated, bifurcation with two stents, length of stent >60mm and chronic total coronary occlusion) or the presence of peripheral artery disease (previous limb revascularization bypass or percutaneous angioplasty, previous limb or foot amputation for arterial vascular disease, history of intermittent claudication of peripheral artery stenosis (≥50%) ,previous carotid revascularization or carotid stenosis ≥50%).
- •Women of childbearing potential with effective contraception defined as
- •combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation :
- •intravaginal
- •transdermal
- •progestogen-only hormonal contraception associated with inhibition of ovulation :
- •injectable
- •implantable
- •intrauterine device (IUD)
- •intrauterine hormone-releasing system ( IUS)
- •bilateral tubal occlusion
- •vasectomised partner
- •sexual abstinence
排除标准
- •Any coronary event within 6 months prior to randomization
- •High risk of bleeding defined as recent (≤6 months) ISTH major bleeding event
- •Constitutional or acquired haemorrhagic disease including gastrointestinal bleeding and thrombocytopenia
- •Planned PCI within the next 6 months after randomization or subject requiring P2Y12 receptor antagonist therapy
- •Stroke within 1 month or any history of hemorrhagic stroke
- •Any contraindication to aspirin (ASA) or any of these excipients or other NSAIDs (hypersensitivity, allergy, active bleeding)
- •Any contraindication to anticoagulant
- •History (s) of asthma induced by the administration of salicylates or substances of close activity (especially NSAIDs)
- •Evolutionary gastroduodenal ulcer
- •Any other gastroduodenal history
- •Severe renal insufficiency
- •Severe hepatic insufficiency
- •Severe, uncontrolled heart failure
- •Lactose intolerance
- •Pregnancy
- •Breastfeeding patients
- •Unable (protected adults : tutorship, curatorship) orunwilling to consent
研究组 & 干预措施
Experimental group
Active Comparator
Patients intaking full-dose OAC + ASA 100mg od
干预措施: OAC + Aspirin 100mg od (Drug)
Control group
Placebo Comparator
Patients intaking full-dose OAC + Placebo of ASA 100mg od
干预措施: OAC + placebo of Aspirin 100mg od (Drug)
结局指标
主要结局
Primary efficacy outcome : rate of composite of cardiovascular mortality and thrombotic cardiovascular events
时间窗: within 24-48 months
The primary efficacy outcome is the incidence of the adjudicated composite of (within 24-48 months): * CV mortality * Thrombotic cardiovascular events * Myocardial infarction * Stroke * Any coronary revascularization * Systemic embolism * Acute limb ischemia An Independent Clinical Events Committee (ICEC) will adjudicate all events (ischemic and bleeding events).
Primary safety outcome : rate of major bleeding
时间窗: within 24-48 months
The primary safety outcome is the occurrence of major bleeding according to the ISTH (International Society of Thrombosis and Haemostasis) definition
次要结局
- Secondary efficacy outcomes : rate of composite of CV mortality, MI, stroke; CV mortality; all cause of death; thrombotic cardiovascular events.(within 24-48 months)
- Secondary safety outcomes : rate of major and clinically relevant non major bleeding(within 24-48 months)
研究者
研究点 (51)
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