AntiPlatelet theraPy stratEgy followiNg Left Atrial appenDAGe closurE
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 60
- 试验地点
- 4
- 主要终点
- Change from baseline of ischaemic lesions number at 3 months appearing on brain MRI scans
研究概览
简要总结
The APPENDAGE study is a phase 4 multicentre randomized opened clinical trial comparing 2 different antithrombotic strategies following left atrial appendage closure (LAAC) in patients with non valvular atrial fibrillation (AF). The primary objective of the study is to evaluate the efficacy of Aspirin versus Aspirin + Clopidogrel after LAAC by comparing the occurrence of ischemic lesions on cerebrovascular magnetic resonance imaging (MRI) studies.
详细描述
Atrial fibrillation (AF) is the most common sustained arrhythmia and increases the risk of ischemic stroke. Although oral anticoagulation (OAC) is recommended in patients with CHADS2VA2SC score ≥ 1, this medication is associated with severe haemorrhagic complications. Several trials showed that percutaneous LAAC with the Watchman device (Boston Scientific, Natick, Massachusetts) or the Amplatzer Cardiac Plug (ACP) /Amulet device (St. Jude Medical, Minneapolis, Minnesota) was shown to be non-inferior but also superior as compared to warfarin in preventing the combined outcome of stroke, systemic embolism, and cardiovascular death. Therefore, LAAC has become an integral part of treatment guidelines in AF patients.
However, the post procedural management of antithrombotic therapy in these patients remains a challenge, as bleeding risk needs to be balanced against risk for thrombus formation on the device and thromboembolic complications. After LAAC, various antithrombotic protocols have been proposed by different teams but the optimal postprocedural antithrombotic medication and its duration are still debated. The Investigators recently showed in a prospective registry that LAAC using ACP devices followed by a single antiplatelet therapy could be a reasonable alternative for stroke prevention in patients with high bleeding risk.
The APPENDAGE study is a phase 4 multicentre randomized opened clinical trial comparing 2 different antithrombotic strategies (aspirin versus aspirin + clopidogrel) following LAAC. The primary objective of the study is to evaluate the efficacy of these 2 strategies after LAAC by comparing the occurrence of ischemic lesions on cerebrovascular MRI studies performed immediately after the procedure (D 0) and after 3 months of follow-up.
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
- 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
- •Male or female patients with LAAC indication according to "Commission nationale d'évaluation des dispositifs médicaux et des technologies de santé" (CNEDiMTS) (National Commission for the Evaluation of Medical Devices and Health Technologies) guidelines
- •Age ≥ 18 years
- •Written informed consent provided by the patient
- •Heart team approval: multidisciplinary team including interventional cardiologists, neurologists and other physicians discussing the definitive contraindication for anticoagulation
- •Registration under social security system
排除标准
- •Unacceptable bleeding risk with double antiplatelet therapy decided by the physician who contraindicated oral anticoagulation
- •LAAC contraindication : left appendage thrombus
- •Major disease resulting in a life expectancy of < 1 year
- •Severe and inherited bleeding disorder
- •Known hypersensitivity to aspirin and/or clopidogrel:
- •Hypersensitivity to clopidogrel, acetylsalicylic acid, or one of the excipients or other nonsteroidal anti-inflammatory drugs (cross-reaction).
- •Asthma or a history of asthma with or without nasal polyps induced by salicylates or substances of close activity, including nonsteroidal anti-inflammatory drugs.
- •Evolving peptic ulcer or history of gastric hemorrhage or perforation after treatment with acetylsalicylic acid or other nonsteroidal anti-inflammatory drugs.
- •Any constitutional or acquired haemorrhagic disease.
- •Patients with mastocytosis, in whom the use of acetylsalicylic acid can lead to severe hypersensitivity reactions (including circulatory shocks with flushing, hypotension, tachycardia and vomiting).
- •Severe liver failure.
- •Severe kidney failure (Creatinine light < 30ml/min).
- •Uncontrolled severe heart failure
- •Contraindication to MRI: claustrophobia or inability to lie still for exam time, implantable pacemaker or defibrillator, intracorporeal metal foreign body (especially intraocular), intracranial metal clip, cochlear implant, cardiac valve prosthesis type Starr-Edwards pre 6000, or biomedical device type insulin pump or neurostimulator.
- •Guardianship
- •Curatorship
- •Pregnancy or child-bearing potential female
- •Woman of childbearing age who does not benefit from highly effective contraception (CTFG recommendation on highly effective contraceptive methods: oral, intravaginal or transdermal estrogeno-progestin contraception; progestin-based oral, injectable or implantable contraception; intrauterine device; hormonal intrauterine device; female sterilization (occlusion of the fallopian tubes))
- •Iode contraindication
- •Patient already participating in another category 1 interventional research
- •Patient in a period of exclusion relative to another research protocol.
研究组 & 干预措施
Aspirin group
Patients randomized in this group: will receive 1 bag containing aspirin 160 mg as treatment. This treatment will start on the day of LAAC procedure and continued for 3 months.
干预措施: Aspirin (Drug)
Aspirin group
Patients randomized in this group: will receive 1 bag containing aspirin 160 mg as treatment. This treatment will start on the day of LAAC procedure and continued for 3 months.
干预措施: Brain MRI (Device)
Double antiplatelet therapy group
Patient randomized in this group will receive 1 tablet containing clopidogrel 75 mg and 1 bag containing aspirin 160 mg as treatment. This treatment will start on the day of LAAC procedure and continued for 3 months.
干预措施: Double antiplatelet therapy (Drug)
Double antiplatelet therapy group
Patient randomized in this group will receive 1 tablet containing clopidogrel 75 mg and 1 bag containing aspirin 160 mg as treatment. This treatment will start on the day of LAAC procedure and continued for 3 months.
干预措施: Brain MRI (Device)
Double antiplatelet therapy group
Patient randomized in this group will receive 1 tablet containing clopidogrel 75 mg and 1 bag containing aspirin 160 mg as treatment. This treatment will start on the day of LAAC procedure and continued for 3 months.
干预措施: Neurological tests (Other)
Aspirin group
Patients randomized in this group: will receive 1 bag containing aspirin 160 mg as treatment. This treatment will start on the day of LAAC procedure and continued for 3 months.
干预措施: Neurological tests (Other)
结局指标
主要结局
Change from baseline of ischaemic lesions number at 3 months appearing on brain MRI scans
时间窗: Baseline and 3 months
Assessment of number of ischaemic lesions appearing on diffusion sequences and/or (Fluid Attenuated Inversion Recovery) FLAIR between cerebral MRI scans at D0 after implantation and after 3 months of antithrombotic treatment. The interpretation of the MRI scans will be centralised and carried out by an independent Corelab in the neuro radiology imaging department of Bordeaux University Hospital. These analyses will be carried out by two independent radiologists. In the event of disagreements or inconsistent values, a third review will be carried out by a third independent radiologist. The final value of the different variables will be reduced to the average of these 2 or 3 interpretations.
次要结局
- Occurrence of symptomatic cerebral ischaemic events(From day 1 to month 3)
- Assessment by the NIHSS scale (National Institute of Health Stroke Score) of the functional impact of ischaemic and/or haemorrhagic strokes(Day 1 and month 3)
- Cognitive assessment by the Montreal Cognitive Assessment (MoCA) scale(Day 1 and Month 3)
- Occurence of device-related thrombus, persistence of a residual leak and endothelialisation process(Month 3)
- Occurrence of systemic thromboembolic events(From day 1 to month 3)
- Occurrence of cerebral haemorrhagic events(From day 0 to month 3)
- Occurence of systemic bleeding events(From day 1 to month 3)
- Assessment by the Modified Rankin Score of the functional impact of ischaemic and/or haemorrhagic strokes(Day 1 and month 3)
- Occurrence of procedural related complications(From day 0 to month 3)
- Counting of treatments taken(Month 3)