Encore PFO Closure Device - The PerFOrm Trial

Study Overview
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Brief Summary
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The objective of this study is to establish reasonable assurance of safety, effectiveness, and noninferiority of the Encore PFO closure device when compared to any investigator chosen FDA-approved PFO closure device.

Detailed Description
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This is a prospective, multicenter, randomized clinical study to determine the safety and effectiveness of the Encore PFO closure device, which is indicated for percutaneous, transcatheter closure of a patent foramen ovale (PFO) in patients who have had a cryptogenic stroke due to a presumed paradoxical embolism.

Official Title
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Encore PFO Closure Device U.S. IDE Randomized Trial - The PerFOrm Trial

Conditions
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Patent Foramen Ovale, Cryptogenic Stroke

Intervention / Treatment
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* Device: Encore PFO closure device
* Device: FDA-approved PFO closure device


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of PFO, defined as visualization of microbubbles per TEE in the left atrium within three cardiac cycles from the right atrial opacification demonstrating right-to-left shunting at rest and/or during Valsalva release Cryptogenic stroke within the last 270 days; stroke is defined as acute focal neurological deficit, presumed to be due to focal ischemia, and confirmed by MRI or CT to be a new, neuroanatomically relevant cerebral infarct Exclusion Criteria: Age <18 years and age >60 years Greater than 50% lumen diameter stenosis of intracranial or extracranial vessels Intracardiac thrombus or tumor Acute or recent (within 6 months) myocardial infarction (MI) or unstable angina Left ventricular aneurysm or akinesis Mitral valve stenosis (mitral valve area less than 1.5cm2) or severe mitral regurgitation Aortic valve stenosis (gradient >40 mmHg) or severe aortic valve regurgitation Mitral or aortic valve vegetation or prosthesis Left ventricular ejection fraction <35% Other identifiable cause 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 Evidence of a hypercoagulable disorder requiring anticoagulation therapy; this determination will be based on the evaluation of: anticardiolipin antibody (Ab) of the IgG or IgM type, Lupus anticoagulant, B2-glycoprotein-1 Ab, and fasting plasma homocysteine Another source of right-to-left shunts identified at baseline, including an atrial septal defect and/or fenestrated septum Any history of atrial fibrillation/atrial flutter (chronic or intermittent) Active endocarditis or other untreated infections Chronic kidney disease stage 4 or higher or end-stage renal failure requiring dialysis (eGFR less than 30) Severe liver disease (ALT 3X ULN) or documented cirrhosis Lung disease requiring continuous home oxygen Uncontrolled hypertension, defined as sustained elevated blood pressure >160/90 mm Hg on medication Uncontrolled diabetes mellitus, defined as HbA1c greater than 9 (based on most recent test which must have been collected within the last year) Anatomical or physiological structures that do not permit TEE Anticipated need for treatment of structural cardiac defects other than PFO Concomitant cardiac anomalies requiring an operative procedure Hemorrhagic diseases (e.g., coagulopathy, tendency to hemolysis) Hypersensitivity to contrast medium or nickel Contraindication to aspirin or clopidogrel The required sheaths cannot be passed through the relevant vessels for access to the PFO Vulnerable patient (e.g., incarcerated or cognitively challenged adults); see Section 7.2.1 Subject is unable or unwilling to provide informed consent Subject is unable to comply with the protocol Any other clinical reasons for which the patient would not be an appropriate candidate for the study, as determined by the site investigators

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Encore PFO closure device<br> | Device: Encore PFO closure device<br>* The Encore PFO closure device comprises an implant component and a single-use delivery system.<br>|
| Active Comparator: Any FDA-approved PFO closure device chosen by the investigator<br> | Device: FDA-approved PFO closure device<br>* Chosen by the investigator<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: The incidence of device- or procedure-related serious adverse events (SAEs) |  | 6 months | 
| Effectiveness: Effective closure | Defined as shunt grade 0 or I while at rest and during Valsalva as assessed by transesophageal echocardiography (TEE) and bubble study as adjudicated by the echocardiographic core laboratory | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete closure | Defined as shunt grade 0 while at rest and during Valsalva as assessed by TEE and bubble study as adjudicated by the echocardiographic core laboratory | 6 months | 
| Occurrence of recurrent symptomatic cryptogenic non-fatal stroke or cardiovascular death |  | 5 years | 
| Occurrence of transient ischemic attacks (TIA) |  | 5 years | 
| Occurrence of clinically significant new atrial arrhythmia (including atrial fibrillation) |  | 5 years | 
| Occurrence of technical success |  | Procedural | 
| Occurrence of procedural success |  | Procedural | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PFO closure, Stroke