Optimal Anti-Thrombotic Management Following Percutaneous Left Atrial Appendage Occlusion (INTEGRAL)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 234
- 试验地点
- 1
- 主要终点
- Composite endpoint of DRT, TE and major bleeding events
研究概览
简要总结
Optimal antithrombotic therapy after percutaneous left atrial appendage occlusion (LAAO) to prevent device-related thrombosis (DRT) is not well established. The main aim of improving the drug strategy after appendage closure is to synergistically optimize the device-based thromboembolic (TE) prevention without increasing the risk of thrombus formation on device and bleeding events. Short-term dual antiplatelet therapy (DAPT) followed by long-term aspirin monotherapy is a strategy commonly prescribed after LAA occlusion. Nonetheless, a significant number of patients continues to suffer from major bleeding and device-related thrombosis (DRT). Recent data reported that, after percutaneous LAA occlusion, a significant activation of the coagulation system occurs, without evidence of a concomitant platelet activation [1]. However, OAC at full dose is not only contraindicated, but also potentially detrimental in patients with an indication for LAA occlusion, given their high bleeding risk and the resulting unsuitability to long term anticoagulation. Half-dose NOAC may provide improved protection against DRT and TE events, without increasing the risk of bleeding. The recent Assessment of Dual Antiplatelet Therapy Versus Rivaroxaban in AF Patients Treated with Left Atrial Appendage Closure (ADRIFT) study [2] reported a better control of thrombin generation in patients with half-dose rivaroxaban compared to DAPT. Additionally, in a prospective series of 555 AF patients, Della Rocca et al have documented long-term half-dose direct oral anticoagulants (DOAC) to be associated with significant reduction in the risk of the composite endpoint of DRT, TE and major bleeding events compared with a standard antiplatelet based antithrombotic therapy (2).
On the basis of these observations, we designed a randomized study to compare two antithrombotic regimens (long-term half-dose apixaban vs long-term aspirin after 45-days of full-dose apixaban) after successful Watchman implantation.
详细描述
- BACKGROUND:
Optimal antithrombotic therapy after percutaneous left atrial appendage occlusion (LAAO) to prevent device-related thrombosis (DRT) is not well established. The main aim of improving the drug strategy after appendage closure is to synergistically optimize the device-based thromboembolic (TE) prevention without increasing the risk of thrombus formation on device and bleeding events. Short-term dual antiplatelet therapy (DAPT) followed by long-term aspirin monotherapy is a strategy commonly prescribed after LAA occlusion. Nonetheless, a significant number of patients continues to suffer from major bleeding and device-related thrombosis (DRT). Recent data reported that, after percutaneous LAA occlusion, a significant activation of the coagulation system occurs, without evidence of a concomitant platelet activation [1]. However, OAC at full dose is not only contraindicated, but also potentially detrimental in patients with an indication for LAA occlusion, given their high bleeding risk and the resulting unsuitability to long term anticoagulation. Half-dose NOAC may provide improved protection against DRT and TE events, without increasing the risk of bleeding. The recent Assessment of Dual Antiplatelet Therapy Versus Rivaroxaban in AF Patients Treated with Left Atrial Appendage Closure (ADRIFT) study [2] reported a better control of thrombin generation in patients with half-dose rivaroxaban compared to DAPT. Additionally, in a prospective series of 555 AF patients, Della Rocca et al have documented long-term half-dose DOAC to be associated with significant reduction in the risk of the composite endpoint of DRT, TE and major bleeding events compared with a standard, antiplatelet based, antithrombotic therapy (2).
On the basis of these observations, we designed a randomized study to compare two antithrombotic regimens (long-term half-dose apixaban vs long-term aspirin after 45-days of full-dose apixaban) after successful Watchman implantation.
1.1 Safety Antithrombotic drugs, either with antiplatelet and anticoagulation therapy, is currently prescribed after Watchman implantation to prevent thrombus formation on device, which significantly increases the risk of stroke and peripheral thromboembolism. A possible side effect of antiplatelets (aspirin) and anticoagulants is excessive bleeding (hemorrhage), because these drugs increase the time it takes for blood clots to form.
The duration of the LAA occlusion procedure and of the related hospitalization will not be prolonged by this pilot study. 2. STUDY RATIONALE Our primary hypothesis is that long-term half-dose apixaban would be superior to long-term aspirin for the primary endpoint. The primary analysis will be performed on an intention-to-treat (ITT) basis. A post-hoc secondary analysis will also be performed. 3. STUDY OBJECTIVES Composite Primary Endpoint The primary endpoint will be a composite of device-related thrombosis (DRT), thromboembolic events [stroke/transient ischemic attacks (TIA)] and major bleeding events 4. STUDY DESIGN Study Overview Patients will be randomly assigned to long-term half-dose apixaban or long-term aspirin in a 1:1 ratio via a computer-generated system and using block sizes of 16 to 20 patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
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
- •• Men and women ≥18 years of age;
- •Patients who underwent a clinically successful LAA closure procedure with a Watchman device (device implanted without procedural or bleeding complication) within a day or are scheduled to undergo the LAAO procedure
- •Paroxysmal, persistent, or permanent AF patients irrespective of prior antithrombotic treatment are eligible for randomization,
- •Written informed consent obtained from subject and ability for subject to comply with the requirements of the study.
排除标准
- •Two or more clinical characteristics at baseline (age≥80 years, body weight ≤60 kg, serum creatinine ≥1.5 mg/dL) requiring apixaban dosage adjustment;
- •Mechanical heart valves or valvular disease requiring surgery or interventional procedure;
- •Mandatory indication for dual antiplatelet therapy (e.g. recent stent) or single anti-platelet treatment (SAPT) (e.g. high coronary risk);
- •Any contra-indication or known allergy to aspirin or clopidogrel or apixaban;
- •Any mandatory indication for anticoagulation for a reason other than AF (e.g. Pulmonary embolism);
- •Ongoing major bleeding or complicated or recent (<72hours) major surgery;
- •Recent myocardial infarction (<6 weeks);
- •Recent TE event (<6 weeks)
- •Recent Intracranial bleeding (< 6 months);
- •Prasugrel or ticagrelor concomitant use
- •Participating in an investigational drug or another device trial within the previous 30 days;
- •High likelihood of being unavailable for follow-up or psycho-social condition making study participation impractical;
- •Pregnancy or within 48 hours post-partum or breast feeding women;
- •Patient under legal protection.
研究组 & 干预措施
long-term half-dose apixaban (Group hdNOAC)
干预措施: Half-Dose of novel OAC (Drug)
long-term aspirin (Group ASA)
干预措施: Low-dose ASA (Drug)
结局指标
主要结局
Composite endpoint of DRT, TE and major bleeding events
时间窗: 3 years
Composite endpoint of device-related thrombosis, TE and major bleeding events
次要结局
未报告次要终点
研究者
Andrea Natale
Executive Medical director
Texas Cardiac Arrhythmia Research Foundation