Randomised Controlled Trial Comparing the Safety and EfficAcy of the Cocoon PFO Occluder Versus Amplatzer PFO ClosurE Device for Percutaneous Closure of Patent Foramen Ovale in Patients With a History of Stroke or Transient Ischemic Attack A Non-Profit, Single-blind, Investigator Driven Trial
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 1,260
- 主要终点
- Composite endpoint of recurrent ischemic stroke, TIA, or all-cause death at 12 months
研究概览
简要总结
This study is a prospective, multicenter, randomized, controlled, single-blind, investigator-driven, non-profit clinical trial designed to compare the safety and efficacy of the Cocoon PFO Occluder with the Amplatzer PFO Occluder family in patients requiring percutaneous closure of a patent foramen ovale (PFO). Eligible participants are adults with a history of cryptogenic embolic stroke or neurologically confirmed transient ischemic attack (TIA) within the previous 12 months and a PFO suitable for transcatheter closure.
A total of up to 1260 subjects will be enrolled across multiple European centers. Participants will be randomly assigned in a 3:1 ratio to receive either the Cocoon PFO Occluder (experimental group) or an Amplatzer PFO closure device (control group). The procedure will be performed as soon as possible after randomization, preferably within 14 days and no later than 45 days.
The primary endpoint is a non-inferiority comparison of a composite outcome at 12 months, including recurrent ischemic stroke, TIA, or all-cause death. Secondary endpoints include PFO closure rate at 6 months, assessed by echocardiographic imaging, and other measures of safety, device performance, and clinical outcomes.
The study is conducted in a single-blind fashion: patients will not be informed of the device they receive unless they explicitly request this information. Any patient who chooses to be unblinded will continue to participate without affecting eligibility or follow-up, and the date of unblinding will be documented to allow appropriate sensitivity analyses.
This trial aims to provide robust comparative evidence on the clinical performance of the Cocoon PFO Occluder relative to the Amplatzer PFO Occluder to guide optimal device selection in patients with cryptogenic stroke or TIA associated with PFO.
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 (Participant)
盲法说明
The study is single-blind. Participants are masked to the device used (Cocoon vs. Amplatzer). Treating physicians and study staff involved in the procedure are not blinded due to the nature of the intervention. Participants may request unblinding at any time
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with >18 years of age and <65 years of age, regardless of gender
- •Patients with normal or aneurysm type PFO confirmed by imaging examination [Transthoracic Echocardiography (TTE)/ Transesophageal Echocardiography (TOE) or Intracardiac Echocardiography], and who exhibit spontaneous right-to-left shunting or right-to-left shunting during Valsalva maneuver.
- •Patients with history of cryptogenic embolic stroke or transient ischemic attack in the previous 12 months [stroke is defined as acute focal neurological deficit presumed to be due to focal ischemia, and either 1) symptoms persisting 24 hours or greater, or 2) symptoms persisting less than 24 hours but associated with MR or CT findings of a new, neuroanatomically relevant, cerebral infarct. Transient Ischemic Attack is defined as acute focal neurological deficit (defined as focal motor deficit, aphasia, difficulty walking, hemisensory deficit, amaurosis fugax, blindness, or focal visual deficit) presumed due to focal ischemia, lasting between 5 minutes and 24 hours, that is not associated with MR or CT findings of a new cerebral infarct]. The diagnosis of cryptogenic embolic stroke or TIA has to be confirmed by a neurologist.
- •The size of PFO must be amenable to selection of a Cocoon PFO Occluder or Amplatzer PFO closure device.
- •Patients are informed of the nature of the trial and agree to all requirements for participation in the trial, signed the informed consent form, and agreed to complete the follow-up and follow-up examination
排除标准
- •Patients who have definite causes of stroke or transient ischemic attack unrelated to the PFO
- •RLS caused by other causes, such as atrial septal defect or pulmonary arteriovenous shunt
- •Patients with atrial fibrillation/atrial flutter (chronic or intermittent) Intracardiac thrombus or tumor
- •Patients with mitral or aortic valve stenosis or severe regurgitation
- •Mitral or aortic valve vegetation or prosthesis
- •Active endocarditis or other untreated infectious diseases
- •Dilated cardiomyopathy, hypertrophic cardiomyopathy, restrictive cardiomyopathy
- •Left ventricular ejection fraction (LVEF) <35%
- •Left ventricular aneurysm or akinesis Myocardial infarction or unstable angina pectoris within 12 months
- •Previous intracardiac surgery or percutaneous PFO-closure
- •Atherosclerosis or arteriopathy of intra- or extracranial vessels with >50% diameter stenosis in the artery supplying the infarcted territory.
- •Patients with non-embolic cryptogenic stroke (for example lacunar stroke) or with other identifiable causes of stroke, including but not limited to aortic arch plaques (protruding >4 mm into the lumen), large artery atherosclerotic disease, an established cardioembolic source, small-vessel occlusive disease, or arterial dissection
- •Glomerular filtration rate < 30 ml/min/1.73 m2 or with any history of renal dialysis or renal transplantation
- •Severe liver function impairment (alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 3 times the upper limit of normal value）
- •Severe pulmonary disease including pulmonary hypertension (clinical diagnosis)
- •Uncontrollable hypertension or diabetes mellitus
- •Contraindications to anticoagulants or antiplatelet drugs, either before or after the PFO closure procedure
- •Active or planned (within 12 months) pregnancy, or lactating female patients
- •Patients with hypercoagulable states
- •Patients diagnosed with a neurological disease that causes progressive neurological dysfunction
- •Malignant tumors or other serious diseases resulting in a life expectancy of less than 12 months
- •Anatomy in which the device would interfere with intracardiac or vascular structures
- •Psychiatric conditions that may interfere with medical compliance and compliance with follow-up
- •Patient is currently participating in another investigational drug or device study that has not reached its primary endpoint yet
- •Patient with any medical condition that would make him/her inappropriate for treatment as per the current IFU of respective devices or in the opinion of the Investigator
- •Inability to obtain Informed Consent from patient or legally authorized representatives
- •Stroke with poor outcome at time of enrollment (Modified Rankin score >3)
- •Subjects who will not be available for follow up for the duration of the trial
研究组 & 干预措施
Cocoon PFO Occluder - experimental
Participants undergo percutaneous closure of patent foramen ovale (PFO) using the Cocoon PFO Occluder device. The procedure is performed under standard clinical practice. Follow-up includes echocardiographic assessment of PFO closure and routine clinical evaluations. Participants are assigned to the two study arms using a 3:1 randomization scheme (Cocoon PFO Occluder : Amplatzer PFO Occluder).
干预措施: PFO Closure procedure (Device)
Amplatzer PFO Occluder - Control
Participants undergo percutaneous closure of patent foramen ovale (PFO) using the Amplatzer PFO Occluder device, considered the current standard of care. Follow-up includes echocardiographic assessment of PFO closure and routine clinical evaluations. Participants are assigned to the two study arms using a 3:1 randomization scheme (Cocoon PFO Occluder : Amplatzer PFO Occluder).
干预措施: PFO Closure procedure (Device)
结局指标
主要结局
Composite endpoint of recurrent ischemic stroke, TIA, or all-cause death at 12 months
时间窗: 12 months after the procedure
A non-inferiority comparison between the Cocoon PFO Occluder and the Amplatzer PFO Occluder in terms of a composite endpoint including: 1. Recurrent ischemic stroke, defined as an acute focal neurological deficit presumed to result from focal ischemia, with symptoms lasting ≥24 hours, or \<24 hours if accompanied by MRI or CT evidence of a new, anatomically relevant cerebral infarct. 2. Transient ischemic attack (TIA), defined as an acute focal neurological deficit (e.g., focal motor deficit, aphasia, gait disturbance, hemisensory deficit, amaurosis fugax, blindness, or focal visual deficit) presumed due to focal ischemia, lasting between 5 minutes and 24 hours, and not associated with MRI or CT evidence of a new infarct. Clinical evaluation by a neurologist is required. 3. All-cause mortality.
次要结局
- PFO Closure Rate(6 months)
- Composite of Recurrent Ischemic Stroke, TIA, or Death(30 days and 6 months)
- Neurological Death(30 days, 6 months, 12 months)
- Cardiovascular Death(30 days, 6 months, 12 months)
- Recurrent Symptomatic Non-Fatal Stroke(30 days, 6 months, 12 months)
- Serious Adverse Events (SAE)(30 days, 6 months, 12 months)
- Device- or Procedure-Related Serious Adverse Events(30 days, 6 months, 12 months)
- Clinically Significant New Atrial Arrhythmia(30 days, 6 months, 12 months)
- Device Success(Immediately after the procedure)
- Procedural Success(At hospital discharge)
- Change in Monthly Migraine Days(Months 9-12 vs. baseline (3 months before implantation))
- Quality of Life (SF-36 Score)(6 months, 12 months)
- Systemic Embolism(30 days, 6 months, 12 months)
- Possible/Probable Device-Related Allergy(12 months)
- Echocardiographic Markers of Device Endothelialization(At 6 months (±1 month) post-procedure At 12 months (±2 months) post-procedure Additional TOE as clinically indicated through study completion (up to 12 months))
研究者
Giuseppe Tarantini
Professor
Sahajanand Medical Technologies Limited