Low-dose Rivaroxaban Monotherapy Versus Guideline Determined Medication Therapy After Left Atrial Appendage Occlusion: a Randomized, Open-label, Multicentre, Superiority Trial
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 4,220
- 试验地点
- 1
- 主要终点
- Rate of the composite endpoint of any death, any stroke, systemic embolism, and The Bleeding Academic Research Consortium (BARC)-defined 3 or 5 bleeding events
研究概览
简要总结
The increased risk of Atrial fibrillation (AF) regarding thromboembolic stroke is predominantly due to the formation and embolization of clots from within the left atrial appendage (LAA). Percutaneous left atrial appendage occlusion (LAAO) is a nonpharmacological strategy for stroke prevention in patients with AF. Data from randomized trials, including PROTECT-AF, PREVAIL, and Prague-17, have suggested that LAAO has comparable efficacy to warfarin or NOACs. Considering these results, LAAO was recommended by the American College of Cardiology (ACC) and European Society of Cardiology (ESC) guidelines as a non-pharmacological stroke prevention strategy for patients with NVAF who have contraindications or are unsuitable for OAC.
The PROTECT-AF and PREVAIL trials stipulated the use of standardized antithrombotic medications which were designed to minimize the risk of stroke, systemic embolism, or device-related thrombosis. This antithrombotic strategy was subsequently endorsed by the guidelines, briefly, patients with LAAO were discharged on warfarin and aspirin for 45 days post-LAAO, if there was no leak or a leak ≤5 mm under transesophageal echocardiography (TEE) at 45-day follow-up, antithrombotic strategies shall switch to dual antiplatelet therapy (DAPT) until 6 months post-LAAO, and then aspirin thereafter.
Although LAAO was recommended by medical societies, previous patient-level meta-analyses have implied that compared with oral anticoagulation, LAAO had significantly more ischemic strokes, suggesting the inability of LAAO to prevent an ischemic stroke from sources beyond LAA. Will a combined strategy of LAAO and OAC further reduce the risk of stroke? The investigators hypothesized that a long-term low dose-Rivaroxaban (10mg daily) post-LAAO might be a potent supplement to the residue risk of ischemic stroke.
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
- Single (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
- •Non-valvular atrial fibrillation (NVAF) patients with successful left atrial appendage occlusion (LAAO)
- •Eligible for guideline-directed anti-thrombotic therapy
- •Able to understand and provide informed consent and comply with all study medications
排除标准
- •Under the age of 18
- •Unable to give informed consent or currently participating in another trial and not yet at its primary endpoint
- •Patient is a woman who is pregnant or nursing (a pregnancy test must be performed within 7 days prior to the index procedure in women of child-bearing potential according to local practice)
- •Concurrent medical condition with a life expectancy of less than two years
- •Haemodynamical unstable
- •Known contraindication to medications such as heparin, antiplatelet or anticoagulation drugs, or contrast
- •Peridevice leak > 5mm as assessed immediately after LAAO or any other procedure-related complications
- •Comorbidities other than atrial fibrillation that required long term use of anticoagulation (such as implanted mechanical valve)
- •Percutaneous coronary intervention (PCI) within 1 year.
- •The patient had or is planning to have any cardiac or non-cardiac interventional or surgical procedure within 30 days prior to or 60 days after the WATCHMAN device implant (e.g., PCI, cardioversion, cardiac surgery)
- •Ongoing overt bleeding
- •Previous stroke/TIA within 30 days of enrolment
- •Symptomatic carotid artery disease
- •Severe renal insufficiency (CrCl≤30ml/min/1.73m2)
研究组 & 干预措施
Low-dose novel oral anti-coagulation (NOAC)-based anti-thrombotic therapy
HAS-BLED<3: Rivaroxaban 15 mg QD for 3 months, followed by Rivaroxaban 10 mg QD indefinitely
HAS-BLED≥3: Rivaroxaban 10 mg QD for 3 months, followed by Rivaroxaban 2.5 mg bid indefinitely
干预措施: Rivaroxaban 15mg (Drug)
Low-dose novel oral anti-coagulation (NOAC)-based anti-thrombotic therapy
HAS-BLED<3: Rivaroxaban 15 mg QD for 3 months, followed by Rivaroxaban 10 mg QD indefinitely
HAS-BLED≥3: Rivaroxaban 10 mg QD for 3 months, followed by Rivaroxaban 2.5 mg bid indefinitely
干预措施: Rivaroxaban 10mg (Drug)
Low-dose novel oral anti-coagulation (NOAC)-based anti-thrombotic therapy
HAS-BLED<3: Rivaroxaban 15 mg QD for 3 months, followed by Rivaroxaban 10 mg QD indefinitely
HAS-BLED≥3: Rivaroxaban 10 mg QD for 3 months, followed by Rivaroxaban 2.5 mg bid indefinitely
干预措施: Rivaroxaban 2.5mg (Drug)
Guideline determined medication therapy (GDMT)
HAS-BLED<3: Rivaroxaban 15 mg QD + Aspirin 100mg QD for 3 months, then Aspirin 100mg QD indefinitely
HAS-BLED≥3: Aspirin 100mg QD + Clopidogrel 75mg QD for 3 months, then Aspirin 100mg QD indefinitely
干预措施: Rivaroxaban 15mg (Drug)
Guideline determined medication therapy (GDMT)
HAS-BLED<3: Rivaroxaban 15 mg QD + Aspirin 100mg QD for 3 months, then Aspirin 100mg QD indefinitely
HAS-BLED≥3: Aspirin 100mg QD + Clopidogrel 75mg QD for 3 months, then Aspirin 100mg QD indefinitely
干预措施: Aspirin 100mg (Drug)
Guideline determined medication therapy (GDMT)
HAS-BLED<3: Rivaroxaban 15 mg QD + Aspirin 100mg QD for 3 months, then Aspirin 100mg QD indefinitely
HAS-BLED≥3: Aspirin 100mg QD + Clopidogrel 75mg QD for 3 months, then Aspirin 100mg QD indefinitely
干预措施: Clopidogrel 75mg (Drug)
结局指标
主要结局
Rate of the composite endpoint of any death, any stroke, systemic embolism, and The Bleeding Academic Research Consortium (BARC)-defined 3 or 5 bleeding events
时间窗: 24 months post randomization
次要结局
- Rate of the BARC type 3 or 5 bleeding events(45 days, 6, 12, 24 months (Time-to-event))
- Rate of the composite endpoint of any death, any stroke, systemic embolism, and BARC defined 3 or 5 bleeding events(45 days, 6, 12 months (Time-to-event))
- Rate of the composite endpoint of any death, any stroke, systemic embolism(45 days, 6, 12, 24 months (Time-to-event))
- Rate of TIMI defined major bleeding and/or minor bleeding(45 days, 6, 12, 24 months (Time-to-event))
- Rate of ISTH defined major bleeding and/or clinically relevant minor bleeding(45 days, 6, 12, 24 months (Time-to-event))
- Scores of the Modified Rankin Scale (mRS)(45 days, 6, 12, 24 months (Continuous))
- Rate of BARC type 3 bleeding events(45 days, 6, 12, 24 months (Time-to-event))
- Rate of patient adherence to allocated medication(45 days, 6, 12, 24 months (Binary))
- Rate of the composite endpoint of any death, any stroke, systemic embolism, myocardial infarction (MI)(45 days, 6, 12, 24 months (Time-to-event))
- Rate of any death(45 days, 6, 12, 24 months (Time-to-event))
- Rate of myocardial infarction (MI)(45 days, 6, 12, 24 months (Time-to-event))
- Rate of BARC type 2, 3 or 5 bleeding events(45 days, 6, 12, 24 months (Time-to-event))
- Rate of BARC type 5 bleeding events(45 days, 6, 12, 24 months (Time-to-event))
- Rate of GUSTO defined major bleeding and/or minor bleeding(45 days, 6, 12, 24 months (Time-to-event))
- Scores of the National Institutes of Health Stroke Scale (NIHSS) questionnaire(45 days, 6, 12, 24 months (Continuous))
- Scores of the 5-level EQ-5D version (EQ-5D-5L) questionnaire(45 days, 6, 12, 24 months (Continuous))
- Rate of any stroke(45 days, 6, 12, 24 months (Time-to-event))
- Rate of systemic embolism(45 days, 6, 12, 24 months (Time-to-event))
- Rate of BARC type 2 bleeding events(45 days, 6, 12, 24 months (Time-to-event))
研究者
LingTao
Professor in Cardiology, Director of the department of Cardiology
Xijing Hospital