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
Overview
- Phase
- Not Applicable
- Status
- Not yet recruiting
- Sponsor
- Giuseppe Tarantini
- Enrollment
- 1,260
- Primary Endpoint
- Composite endpoint of recurrent ischemic stroke, TIA, or all-cause death at 12 months
Overview
Brief Summary
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 Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Single (Participant)
Masking Description
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
Eligibility Criteria
- Ages
- 18 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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
Exclusion Criteria
- •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
Arms & Interventions
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).
Intervention: 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).
Intervention: PFO Closure procedure (Device)
Outcomes
Primary Outcomes
Composite endpoint of recurrent ischemic stroke, TIA, or all-cause death at 12 months
Time Frame: 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.
Secondary Outcomes
- 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))
Investigators
Giuseppe Tarantini
Professor
Sahajanand Medical Technologies Limited