International PFO Consortium

Sponsor

University Hospital Inselspital, Berne (Other)

Overall Status

Unknown status

CT.gov ID

NCT00859885

Collaborator

University Hospital, Basel, Switzerland (Other), University of Lausanne Hospitals (Other), University Hospital, Geneva (Other), University Hospital, Zürich (Other), Triemli Hospital (Other), Cantonal Hospital of Aarau, Switzerland (Other), Alfried-Krupp Krankenhaus of Essen, Germany (Other), University Hospital, Essen (Other), Klinikum Worms (Other), Tufts Medical Center (Other), Baystate Medical Center (Other), East Medical Center Tyler, Texas (Other), Universitaire Ziekenhuizen Leuven (Other), Ammerland Klinik GmbH, Westerstede, Germany (Other), University Hospital, Ghent (Other), Arcispedale Santa Maria Nuova-IRCCS (Other)

1,500

Enrollment

Locations

158.8

Anticipated Duration (Months)

83.3

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Stroke Transient Ischemic Attack	Drug: Antithrombotic treatment Device: percutaneous device closure of PFO

Detailed Description

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

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.

Study Design

Study Type:

Observational

Anticipated Enrollment :

1500 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

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

Actual Study Start Date :

Sep 8, 2008

Anticipated Primary Completion Date :

Dec 1, 2021

Anticipated Study Completion Date :

Dec 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
1 Patients who receive antithrombotic treatment only	Drug: Antithrombotic treatment antiplatelets, anticoagulants Other Names: aspirin
2 Patients who undergo percutaneous device closure	Device: percutaneous device closure of PFO umbrella device for PFO closure Other Names: clopidogrel

Arm

Intervention/Treatment

Patients who receive antithrombotic treatment only

Drug: Antithrombotic treatment

antiplatelets, anticoagulants

Other Names:

aspirin

Patients who undergo percutaneous device closure

Device: percutaneous device closure of PFO

umbrella device for PFO closure

Other Names:

clopidogrel

Outcome Measures

Primary Outcome Measures

proportion of patients free of any stroke (including fatal stroke) or TIA [3 years]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Tufts Medical Center	Boston	Massachusetts	United States	02111
2	Baystate Medical Center	Springfield	Massachusetts	United States	01199
3	East Medical Center	Tyler	Texas	United States	75710
4	University Hospital Gent	Gent		Belgium	9000
5	Leuven University Hospital	Leuven		Belgium	3000
6	Alfried Krupp Hospital	Essen		Germany	45117
7	Essen University Hospital	Essen		Germany	45147
8	Ammerland Klinik GmbH	Westerstede		Germany	26655
9	Klinikum Worms gGmbH	Worms		Germany	67550
10	Arcispedale Santa Maria Nuova, Department of Neurology, ASMN IRCCS	Reggio Emilia		Italy	42123
11	University Hospital Doctor Josep Trueta	Girona		Spain	17707
12	Cantonal Hospital of Aarau	Aarau		Switzerland	5001
13	Basel University Hospital	Basel		Switzerland	4031
14	Department of Neurology, Bern University Hospital, Bern	Bern		Switzerland	3010
15	Geneva University Hospital	Geneva		Switzerland	1211
16	Lausanne University Hospital	Lausanne		Switzerland	1011
17	Zürich Triemli Hospital	Zürich		Switzerland	8063
18	Zürich University Hospital	Zürich		Switzerland	8091

Investigators

Principal Investigator: Krassen Nedeltchev, MD, Kantonsspital Aarau
Principal Investigator: Marie-Luise Mono, MD, Dep. of Neurology, Bern University Hospital, Bern
Study Director: Marcel Arnold, MD, University of Bern, Inselspital