Clinical trial NCT00859885: International PFO Consortium
Official title: Secondary Stroke Prevention In Patients With Patent Foramen Ovale: International PFO Consortium
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Stroke
Transient Ischemic Attack
Keywords: patent foramen ovale
ischemic stroke
transient ischemic attack
secondary prevention
medical treatment
percutaneous device closure
Lead sponsor: Insel Gruppe AG, University Hospital Bern
Sponsor class: OTHER
Collaborators: name: University Hospital, Basel, Switzerland
name: University of Lausanne Hospitals
name: University Hospital, Geneva
name: University Hospital, Zürich
name: Triemli Hospital
name: Cantonal Hospital of Aarau, Switzerland
name: Alfried-Krupp Krankenhaus of Essen, Germany
name: University Hospital, Essen
name: Klinikum Worms
name: Tufts Medical Center
name: Baystate Medical Center
name: East Medical Center Tyler, Texas
name: Universitaire Ziekenhuizen KU Leuven
name: Ammerland Klinik GmbH, Westerstede, Germany
name: University Hospital, Ghent
name: Azienda USL Reggio Emilia - IRCCS
First posted: 2009-03-11
Enrollment: 1500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with ischemic stroke or transient ischemic attacks, in whom a patent foramen ovale has been diagnosed by means of a transesophageal echocardiography

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.

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.

Eligibility 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

Primary outcomes:
measure: proportion of patients free of any stroke (including fatal stroke) or TIA
timeFrame: 3 years
Secondary outcomes:
measure: influence of gender, age, spontaneous or large shunt, coincidence of an atrial septum aneurysma
timeFrame: 3 years
measure: influence of competitive causes of stroke
timeFrame: 3 years
measure: frequency of residual shunt, (in)correct device position, need for implantation of second device and periprocedural complications
timeFrame: 30 days and 6 months
Other outcomes:
Locations:
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Springfield
country: United States
facility: Baystate Medical Center
state: Massachusetts
city: Tyler
country: United States
facility: East Medical Center
state: Texas
city: Gent
country: Belgium
facility: University Hospital Gent
city: Leuven
country: Belgium
facility: Leuven University Hospital
city: Essen
country: Germany
facility: Alfried Krupp Hospital
city: Essen
country: Germany
facility: Essen University Hospital
city: Westerstede
country: Germany
facility: Ammerland Klinik GmbH
city: Worms
country: Germany
facility: Klinikum Worms gGmbH
city: Reggio Emilia
country: Italy
facility: Arcispedale Santa Maria Nuova, Department of Neurology, ASMN IRCCS
city: Girona
country: Spain
facility: University Hospital Doctor Josep Trueta
city: Aarau
country: Switzerland
facility: Cantonal Hospital of Aarau
city: Basel
country: Switzerland
facility: Basel University Hospital
city: Bern
country: Switzerland
facility: Department of Neurology, Bern University Hospital, Bern
city: Geneva
country: Switzerland
facility: Geneva University Hospital
city: Lausanne
country: Switzerland
facility: Lausanne University Hospital
city: Zürich
country: Switzerland
facility: Zürich Triemli Hospital
city: Zürich
country: Switzerland
facility: Zürich University Hospital
Study officials:
affiliation: Kantonsspital Aarau
name: Krassen Nedeltchev, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Dep. of Neurology, Bern University Hospital, Bern
name: Marie-Luise Mono, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Bern, Inselspital
name: Marcel Arnold, MD
role: STUDY_DIRECTOR
References: