International PFO Consortium

Study Overview
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Brief Summary
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The prevalence of patent foramen ovale (PFO) is about 25% in the general population and approximately 40% in patients who have ischemic stroke of unknown cause (cryptogenic stroke). Given the large number of asymptomatic patients, no primary prevention is currently recommended. On the contrary, secondary prevention is very important. Prospective studies have shown that antithrombotic treatment (ATT) with aspirin or warfarin appears to negate the risk of recurrent stroke associated with a PFO. Patients with spontaneous or large right-to-left shunts (RLS), those with a coinciding atrial septal aneurysm (ASA) or multiple ischemic events prior to the PFO diagnosis may still be at increased risk of stroke recurrence despite ATT. Percutaneous device closure (PDC) is a challenging alternative to ATT. Several studies reported 0% to 3.4% annual recurrence rates of stroke or TIA in patients treated by PDC. To date, there is no data from randomized controlled trials (RCT) comparing the risk of stroke recurrence after PDC with that under ATT only. The results from ongoing RCTs are not to be awaited in the near future, mainly due to low enrolment and event rates. Alternative data-gathering strategies such as multicenter registries are needed to overcome the low recruitment rates. The aim of the present study is to compare the risk of recurrent stroke and TIA in patients with PFO and otherwise unexplained stroke who undergo PDC or receive ATT.

Detailed Description
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Background The prevalence of patent foramen ovale (PFO) is about 25% in the general population and approximately 40% in patients who have ischemic stroke of unknown cause (cryptogenic stroke). Given the large number of asymptomatic patients, no primary prevention is currently recommended. On the contrary, secondary prevention is very important. Prospective studies have shown that antithrombotic treatment (ATT) with aspirin or warfarin appears to negate the risk of recurrent stroke associated with a PFO. Patients with spontaneous or large right-to-left shunts (RLS), those with a coinciding atrial septal aneurysm (ASA) or multiple ischemic events prior to the PFO diagnosis may still be at increased risk of stroke recurrence despite ATT. Percutaneous device closure (PDC) is a challenging alternative to ATT. Several studies reported 0% to 3.4% annual recurrence rates of stroke or TIA in patients treated by PDC. To date, there is no data from randomized controlled trials (RCT) comparing the risk of stroke recurrence after PDC with that under ATT only. The results from ongoing RCTs are not to be awaited in the near future, mainly due to low enrolment and event rates. Even if RCTs are completed successfully, statistical differences may remain undetected with the planned sample sizes. Alternative data-gathering strategies such as multicenter registries are needed to overcome the low recruitment rates. Objective 1) To compare the risk of recurrent stroke and TIA in patients aged ≤ 55 years with PFO and otherwise unexplained stroke who undergo PDC or receive ATT only; 2) To assess the etiological role of PFO for stroke/TIA in patients aged > 55 years; 3) To assess the risk of recurrent stroke/TIA in high-risk PFO patients (i.e. those with spontaneous (at rest) or large RLS, coinciding ASA, or multiple previous cerebrovascular events). Methods Multicenter prospective non-randomized study with scheduled 3-years follow-up of patients with PFO and ischemic stroke or TIA. Participating centers: Swiss University Hospitals of Basel, Bern, Geneva, Lausanne and Zurich, the Cantonal Hospital of Aarau, the Triemli Hospital, the Alfried-Krupp Krankenhaus of Essen, the University Hospital of Essen, the Klinikum Worms gGmbH, Tufts Medical Center, Baystate Medical Center, the East Medical Center Tyler, and the University Hospital of Leuven.

Official Title
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Secondary Stroke Prevention In Patients With Patent Foramen Ovale: International PFO Consortium

Conditions
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Stroke, Transient Ischemic Attack

Intervention / Treatment
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* Drug: Antithrombotic treatment
* Device: percutaneous device closure of PFO


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 18 years Diagnosis of PFO established by transesophageal echocardiography (TEE) Ischemic stroke or transient ischemic attack within the previous 6 months Exclusion Criteria Non-vascular origin of the neurological symptoms after brain imaging (CT scan or MRI) Comorbid condition that would interfere with the study Pregnancy History of intracranial bleeding, confirmed arterio-venous malformation, aneurysm or uncontrolled coagulopathy Contraindications for TEE, echocardiographic or iodine contrast media

Ages Eligible for Study
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Minimum Age: 18 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 1<br>Patients who receive antithrombotic treatment only | Drug: Antithrombotic treatment<br>* antiplatelets, anticoagulants<br>* Other names: aspirin;|
| 2<br>Patients who undergo percutaneous device closure | Device: percutaneous device closure of PFO<br>* umbrella device for PFO closure<br>* Other names: clopidogrel;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| proportion of patients free of any stroke (including fatal stroke) or TIA |  | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| influence of gender, age, spontaneous or large shunt, coincidence of an atrial septum aneurysma |  | 3 years | 
| influence of competitive causes of stroke |  | 3 years | 
| frequency of residual shunt, (in)correct device position, need for implantation of second device and periprocedural complications |  | 30 days and 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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patent foramen ovale, ischemic stroke, transient ischemic attack, secondary prevention, medical treatment, percutaneous device closure