International PFO Consortium

Condition(s) targeted: Stroke; Transient Ischemic Attack

Intervention: Antithrombotic treatment (Drug); percutaneous device closure of PFO (Device)

Phase: N/A

Status: Recruiting

Sponsored by: University Hospital Inselspital, Berne

Official(s) and/or principal investigator(s):
Krassen Nedeltchev, MD, Principal Investigator, Affiliation: Kantonsspital Aarau
Marie-Luise Mono, MD, Principal Investigator, Affiliation: Dep. of Neurology, Bern University Hospital, Bern
Marcel Arnold, MD, Study Director, Affiliation: University of Bern, Inselspital

Overall contact:
Krassen Nedeltchev, MD, Phone: +41 62 838 66 75, Email: Krassen.Nedeltchev@ksa.ch

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.

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

Study design: Observational Model: Cohort, Time Perspective: Prospective

Primary outcome: proportion of patients free of any stroke (including fatal stroke) or TIA

Secondary outcome:

influence of gender, age, spontaneous or large shunt, coincidence of an atrial septum aneurysma

influence of competitive causes of stroke

frequency of residual shunt, (in)correct device position, need for implantation of second device and periprocedural complications

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 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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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

Krassen Nedeltchev, MD, Phone: +41 62 838 66 75, Email: Krassen.Nedeltchev@ksa.ch

University Hospital Gent, Gent 9000, Belgium; Recruiting
Dimitri Hemelsoet, MD

Leuven University Hospital, Leuven 3000, Belgium; Recruiting

Alfried Krupp Hospital, Essen 45117, Germany; Recruiting

Essen University Hospital, Essen 45147, Germany; Recruiting

Ammerland Klinik GmbH, Westerstede 26655, Germany; Recruiting
Andreas Müller-Eichelberg, MD

Klinikum Worms gGmbH, Worms 67550, Germany; Recruiting

University Hospital Doctor Josep Trueta, Girona 17707, Spain; Recruiting
Joaquín Serena, MD

Cantonal Hospital of Aarau, Aarau 5001, Switzerland; Recruiting

Basel University Hospital, Basel 4031, Switzerland; Recruiting

Department of Neurology, Bern University Hospital, Bern, Bern 3010, Switzerland; Recruiting
Marie-Luise Mono, Phone: +41316320743, Email: marie-luise.mono@insel.ch
Marie-Luise Mono, MD, Principal Investigator
Bernhard Meier, MD, Sub-Investigator
Marcel Arnold, MD, Sub-Investigator

Geneva University Hospital, Geneva 1211, Switzerland; Recruiting

Lausanne University Hospital, Lausanne 1011, Switzerland; Recruiting

Zürich Triemli Hospital, Zürich 8063, Switzerland; Recruiting

Zürich University Hospital, Zürich 8091, Switzerland; Recruiting

Tufts Medical Center, Boston, Massachusetts 02111, United States; Recruiting

Baystate Medical Center, Springfield, Massachusetts 01199, United States; Recruiting

Arcispedale Santa Maria Nuova, Department of Neurology, ASMN IRCCS, Reggio Emilia 42123, Italy; Recruiting

East Medical Center, Tyler, Texas 75710, United States; Recruiting

Starting date: January 2009
Last updated: September 8, 2014