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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
1,260
Percutaneous PFO closure performed according to standard clinical practice. The procedure is scheduled within 45 days after randomization and includes initiation of dual antiplatelet therapy before the intervention. Closure is performed following the Instructions for Use (IFU) of the assigned device and is guided by intracardiac echocardiography or transesophageal echocardiography. After device implantation, patients undergo routine post-procedure assessment and are instructed to follow antiplatelet therapy consistent with European clinical practice guidelines. Endocarditis prophylaxis is recommended for six months. The procedural steps are identical for both study arms; the only difference is the device implanted (Cocoon PFO Occluder or Amplatzer PFO Occluder). Participants are assigned to the two study arms using a 3:1 randomization scheme (Cocoon PFO Occluder : Amplatzer PFO Occluder).
Composite endpoint of recurrent ischemic stroke, TIA, or all-cause death at 12 months
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.
Time frame: 12 months after the procedure
PFO Closure Rate
Complete closure is defined as right-to-left shunt (RLS) grade 0. Effective closure is defined as RLS grade 0 or 1 on imaging (TTE as default, TOE when clinically indicated)
Time frame: 6 months
Composite of Recurrent Ischemic Stroke, TIA, or Death
Composite endpoint including recurrent ischemic stroke, TIA (neurologist-confirmed), or all-cause mortality.
Time frame: 30 days and 6 months
Neurological Death
Death attributable to neurological causes.
Time frame: 30 days, 6 months, 12 months
Cardiovascular Death
Death attributable to cardiovascular causes.
Time frame: 30 days, 6 months, 12 months
Recurrent Symptomatic Non-Fatal Stroke
TIA defined according to the same criteria as the primary endpoint and confirmed by a neurologist
Time frame: 30 days, 6 months, 12 months
Serious Adverse Events (SAE)
Incidence of any serious adverse event as defined by standard reporting criteria.
Time frame: 30 days, 6 months, 12 months
Device- or Procedure-Related Serious Adverse Events
SAE related to the device or procedure, including but not limited to: death, systemic embolism, device embolization or malposition, device thrombosis, cardiac injury/perforation, pericardial tamponade/effusion, endocarditis, atrial fibrillation, and severe vascular access complications
Time frame: 30 days, 6 months, 12 months
Clinically Significant New Atrial Arrhythmia
New atrial arrhythmia (including AF) confirmed by ECG, Holter, or approved monitoring device. AF defined per international guidelines (≥30-second episode with absence of P waves and irregular RR intervals).
Time frame: 30 days, 6 months, 12 months
Device Success
Successful delivery, deployment at intended site, and retrieval of the delivery system.
Time frame: Immediately after the procedure
Procedural Success
Device success without device- or procedure-related SAE prior to discharge
Time frame: At hospital discharge
Change in Monthly Migraine Days
Change in monthly migraine days in patients with a neurologist-confirmed diagnosis of migraine.
Time frame: Months 9-12 vs. baseline (3 months before implantation)
Quality of Life (SF-36 Score)
Assessment of quality of life using the SF-36 questionnaire.
Time frame: 6 months, 12 months
Systemic Embolism
Incidence of systemic embolic events confirmed clinically or by imaging
Time frame: 30 days, 6 months, 12 months
Possible/Probable Device-Related Allergy
Device-related allergic reactions adjudicated by the Clinical Events Committee (CEC)
Time frame: 12 months
Echocardiographic Markers of Device Endothelialization
Evaluation of endothelialization using surrogate TOE markers: device surface echogenicity, peri-device flow, presence of thrombus/mass, visible disc surface area, and bubble contrast washout. Data will be summarized as the proportion of participants meeting criteria for complete endothelialization at each follow-up time point.
Time frame: 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)
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.