International PFO Consortium

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

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.

Study Overview

• Status: Unknown
• Conditions: Stroke; Transient Ischemic Attack
• Intervention / Treatment: 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

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.

• Study Type: Observational
• Enrollment (Anticipated): 1500

Contacts and Locations

Study Locations

• Belgium
  • Gent, Belgium, 9000
    • Recruiting
    • University Hospital Gent
    • Contact: Dimitri Hemelsoet, MD
  • Leuven, Belgium, 3000
    • Recruiting
    • Leuven University Hospital
• Germany
  • Essen, Germany, 45117
    • Recruiting
    • Alfried Krupp Hospital
  • Essen, Germany, 45147
    • Recruiting
    • Essen University Hospital
  • Westerstede, Germany, 26655
    • Recruiting
    • Ammerland Klinik GmbH
    • Contact: Andreas Müller-Eichelberg, MD
  • Worms, Germany, 67550
    • Recruiting
    • Klinikum Worms gGmbH
• Italy
  • Reggio Emilia, Italy, 42123
    • Recruiting
    • Arcispedale Santa Maria Nuova, Department of Neurology, ASMN IRCCS
• Spain
  • Girona, Spain, 17707
    • Recruiting
    • University Hospital Doctor Josep Trueta
    • Contact: Joaquín Serena, MD
• Switzerland
  • Aarau, Switzerland, 5001
    • Recruiting
    • Cantonal Hospital of Aarau
  • Basel, Switzerland, 4031
    • Completed
    • Basel University Hospital
  • Bern, Switzerland, 3010
    • Recruiting
    • Department of Neurology, Bern University Hospital, Bern
    • Contact: Marie-Luise Mono; Phone Number: +41316320743; Email: marie-luise.mono@insel.ch
    • Principal Investigator: Marie-Luise Mono, MD
    • Sub-Investigator: Bernhard Meier, MD
    • Sub-Investigator: Marcel Arnold, MD
  • Geneva, Switzerland, 1211
    • Recruiting
    • Geneva University Hospital
  • Lausanne, Switzerland, 1011
    • Recruiting
    • Lausanne University Hospital
  • Zürich, Switzerland, 8063
    • Completed
    • Zürich Triemli Hospital
  • Zürich, Switzerland, 8091
    • Recruiting
    • Zurich University Hospital
• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Recruiting
      • Tufts Medical Center
    • Springfield, Massachusetts, United States, 01199
      • Completed
      • Baystate Medical Center
  • Texas
    • Tyler, Texas, United States, 75710
      • Recruiting
      • East Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: University Hospital Inselspital, Berne
• Collaborators: University Hospital, Geneva; Universitaire Ziekenhuizen KU Leuven; University Hospital, Essen; University Hospital, Basel, Switzerland; Tufts Medical Center; University Hospital, Ghent; University of Lausanne Hospitals; University Hospital, Zürich; Baystate Medical Center; Cantonal Hospital of Aarau, Switzerland; Triemli Hospital; Arcispedale Santa Maria Nuova-IRCCS; Alfried-Krupp Krankenhaus of Essen, Germany; Klinikum Worms; East Medical Center Tyler, Texas; Ammerland Klinik GmbH, Westerstede, Germany
• 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

Study record dates

Study Major Dates

• Study Start (Actual): September 8, 2008
• Primary Completion (Anticipated): December 1, 2021
• Study Completion (Anticipated): December 1, 2021

Study Registration Dates

• First Submitted: March 6, 2009
• First Submitted That Met QC Criteria: March 10, 2009
• First Posted (Estimate): March 11, 2009

Study Record Updates

• Last Update Posted (Actual): December 12, 2017
• Last Update Submitted That Met QC Criteria: December 11, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Keywords: ischemic stroke; secondary prevention; transient ischemic attack; medical treatment; patent foramen ovale; percutaneous device closure
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Ischemia; Stroke; Ischemic Attack, Transient; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Clopidogrel
• Other Study ID Numbers: 117/08