Transcatheter Patent Foramen Ovale (PFO) Closure, Oral Anticoagulants or Antiplatelet Therapy After PFO-associated Stroke in Patients Between 60 and 80 Years Old : a Randomised Controlled Trial.
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 792
- 试验地点
- 42
- 主要终点
- Time to recurrent stroke (ischemic or hemorrhagic fatal or non-fatal)
研究概览
简要总结
To assess whether PFO closure plus antiplatelet therapy is superior to antiplatelet therapy alone and whether oral anticoagulant therapy is superior to antiplatelet therapy to prevent stroke recurrence in patients aged 60 to 80 years with a PFO with large shunt (> 20 microbubbles) or a PFO associated with an ASA (> 10 mm), and an otherwise unexplained ischemic stroke.
详细描述
The CLOSE trial (NCT00562289, NEJM 2017) has unambiguously demonstrated the superiority of patent foramen ovale (PFO) closure over antiplatelet therapy alone in patients aged up to 60 years with a PFO associated with an atrial septal aneurysm (ASA) or a large right-to-left shunt (so-called "high-risk PFO"), and an otherwise unexplained ischemic stroke. Oral anticoagulant therapy is also a logical approach assuming that PFO-related strokes are due to paradoxical embolism which implies a venous source of embolism, or to direct embolization of a thrombus formed at the atrial level. The CLOSE trial also suggested that oral anticoagulants might reduce stroke recurrence compared to aspirin.
There is accumulating evidence that presence of a PFO is significantly associated with cryptogenic stroke in patients over 60 years. Cryptogenic ischemic strokes represent about one third of all ischemic strokes in patients older than 60 years. However, the optimal therapeutic strategy in patients older than 60 years with a PFO and an otherwise unexplained ischemic stroke is unknown, because these patients were excluded from randomized trials.
The hypothesis tested in this trial is that transcatheter PFO closure plus long-term antiplatelet therapy is superior to antiplatelet therapy alone and that oral anticoagulant therapy is superior to antiplatelet therapy to prevent recurrent stroke in patients aged 60 to 80 years who have a high-risk PFO and a recent otherwise unexplained 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
- Prevention
- 盲法
- Single (Outcomes Assessor)
盲法说明
The clinical event adjudication committee will blind to the treatment allocated by randomization.
入排标准
- 年龄范围
- 60 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Man or woman aged 60 to 80 years.
- •Recent (≤ 6 months) ischemic stroke confirmed by cerebral imaging regardless of symptom duration.
- •Absence of a more probable cause of stroke than PFO after a standardized etiological work-up (see addenda).
- •Presence of a PFO with at least 1 of the 2 following characteristics:
- •PFO with large shunt (> 20 microbubbles) appearing in the left atrium during at least one of the 3 cardiac cycles after complete opacification of the right atrium, detected either spontaneously or during provocative manoeuvers, on contrast transthoracic (TTE) or transoesophageal (TOE) echocardiography. The diagnosis of PFO by contrast TEE must be confirmed by contrast TOE showing a right-to-left passage of the contrast material across the PFO.
- •PFO associated with an ASA on transoesophageal echocardiography: excursion >10 mm
- •Affiliation to a French Health Insurance system. Informed consent.
排除标准
- •Life expectancy < 4 years.
- •Contraindication to both experimental treatments (PFO closure, oral anticoagulant therapy) or to the reference treatment (antiplatelet therapy) (see paragraph 20.5).
- •Indication to long-term anticoagulant therapy.
- •Presence of other medical conditions that would lead to inability to complete the study or interfere with the assessment of outcomes.
- •Previous surgical or transcatheter treatment of PFO or ASA. Expected impossible follow-up or poor compliance.
- •PFO associated with an atrial septal defect (ASD) requiring closure (significant shunt with impact on the right cavities, elevation of pulmonary pressures or QP/QS>2)
- •Patient unable to understand the informed consent form. Patient under tutorship, curatorship, or legal protection.
研究组 & 干预措施
Antiplatelet therapy
Aspirin OR clopidogrel
干预措施: Antiplatelet therapy (Drug)
Oral anticoagulants, Direct-Acting
Apixaban (5mg twice a day) OR Dabigatran (150 mg twice a day) OR Rivaroxaban (20 mg once a day)
干预措施: Oral Anticoagulant, Direct-Acting (Drug)
PFO closure
PFO closure followed by dual antiplatelet therapy (aspirin 75 mg/d + clopidogrel 75 mg/d) for 3 months, then by single antiplatelet therapy by aspirin or clopidogrel
干预措施: Transcatheter PFO closure (Procedure)
PFO closure
PFO closure followed by dual antiplatelet therapy (aspirin 75 mg/d + clopidogrel 75 mg/d) for 3 months, then by single antiplatelet therapy by aspirin or clopidogrel
干预措施: Antiplatelet therapy (Drug)
结局指标
主要结局
Time to recurrent stroke (ischemic or hemorrhagic fatal or non-fatal)
时间窗: From date of randomization until the date of first recurrent stroke, assessed from up to 4 years (for the last patient included) to up to 8 years (for the first patient included)
Stroke: sudden onset of focal neurological symptoms related to a disturbance of the cerebral circulation. Ischemic stroke : at least one of the following criteria: * Sudden onset of focal neurological symptoms with the presence of cerebral infarction in the appropriate territory on brain imaging (CT or MRI), regardless of the duration of symptoms (less than or more than 24 hours). * Sudden onset of focal neurological symptoms lasting more than 24 hours, with no apparent cause other than cerebral ischemia. Intracerebral hemorrhage: sudden onset of focal neurological symptoms with the presence of cerebral hemorrhage in the appropriate territory on brain imaging (CT or MRI), regardless of the duration of symptoms (less than or more than 24 hours) and regardless of the cause of the hemorrhage (spontaneous or secondary to trauma, tumour or another cause). Unknown type of stroke : the type of stroke cannot be determined with certainty and the symptoms last more than 24 hours.
次要结局
- Time to disabling stroke(From date of randomization until the date of first recurrent disabling stroke, assessed from up to 4 years (for the last patient included) to up to 8 years (for the first patient included))
- Time to ischemic stroke(From date of randomization until the date of first recurrent ischemic stroke, assessed from up to 4 years (for the last patient included) to up to 8 years (for the first patient included))
- Time to ischemic stroke or systemic embolism(From date of randomization until the date of first recurrent ischemic stroke or systemic embolism, assessed from up to 4 years (for the last patient included) to up to 8 years (for the first patient included))
- Time to all-cause mortality(From date of randomization until the date of death, assessed from up to 4 years (for the last patient included) to up to 8 years (for the first patient included))
- Proportion of success of device implantation, of the procedure and of PFO closure,(6 months after PFO closure)
- Proportion of fatal, life-threatening or major procedure- or device-related complications(Within 4 weeks following the procedure (PFO closure))
- Incremental cost-utility ratio at 4 years (ICUR)(Within 48 months after randomization)
- Time to transient ischemic attack,(From date of randomization until the date of first transient ischemic attack, assessed from up to 4 years (for the last patient included) to up to 8 years (for the first patient included))
- Time to vascular death(From date of randomization until the date of vascular death, assessed from up to 4 years (for the last patient included) to up to 8 years (for the first patient included))
- Quality of life score(Every 6 months after randomization or up to 4 years (for the last patient included) to up to 8 years (for the first patient included)])
- Time to ischemic stroke recurrence according to the presence of a residual shunt(From date of PFO closure until the date of first ischemic stroke recurrence, assessed from up to 4 years (for the last patient included) to up to 8 years (for the first patient included), according to the presence of residual shunt])
- Time to fatal, life-threatening or major hemorrhage, including intracerebral and Intracranial hemorrhage(From date of randomization until the date of first fatal,life-threatening or major hemorrhage,including intracerebral and Intracranial hemorrhage,assessed from up to 4 years(for the last patient included) to up to 8 years(for the first patient included))
- Time to new-onset atrial fibrillation(From date of randomization until the date of new-onset atrial fibrillation, assessed from up to 4 years (for the last patient included) to up to 8 years (for the first patient included)])
- Costs(Within 48 months after randomization)