Official Title: “Closure of Patent Foramen Ovale or Anticoagulants Versus Antiplatelet Therapy to Prevent Stroke Recurrence”

A patent foramen ovale (PFO) is found more frequently in patients with an ischemic stroke than in control subjects.

Therapeutic options to prevent stroke recurrence include antiplatelet drugs, oral anticoagulants, and transcatheter closure of the foramen. However, there are no published studies showing convincingly the superiority of any one of these strategies in preventing stroke recurrence.

The aim of this randomized clinical trial is to assess whether chronic anticoagulation on the one hand and transcatheter on the other hand are superior to chronic antiplatelet therapy in preventing stroke recurrence.

Study Type: Interventional

Study Design: Prevention, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: December 2012

Secondary prevention for stroke patients with PFO is a subject of considerable debate.

Therapeutic options include antiplatelet drugs, oral anticoagulants, and transcatheter closure of the foramen. There are no published studies showing convincingly the superiority of any one of these strategies in preventing stroke recurrence. All the therapeutic options have some risks and unless randomised trials can define who should be treated with what (if anything), and for how long, we could end up exposing patients to unnecessary complications of treatment.

The primary objective of this study is to assess whether chronic anticoagulation (INR 2 to 3) on the one hand and endovascular treatment on the other hand are superior to chronic antiplatelet therapy in preventing stroke recurrence in young (16 to 60 years) patients with a PFO (> 30 microbubbles or associated with an atrial septal aneurysm) and an otherwise unexplained ischaemic stroke.

Secondary objectives of the study are: - to evaluate the safety of the three therapeutic options, in terms of major drug-, device- or procedure-related complications, in order to allow a benefit/risk assessment of each therapeutic option in this population. - to assess the rate of technical success and effectiveness of endovascular procedure to treat PFO and ASA.

Intervention(s) in this Clinical Trial

• Drug: aspirin
  • during the follow up
• Drug: Antivitamins K
  • during the follow up
• Device: Devices for PFO closure
  • endovascular treatment no longer than 21 days after the random.

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 1
• Experimental: 2
• Experimental: 3

Primary Measures

• stroke(fatal or not)
  • Time Frame: during the follow up (between 3 or 5 years)
    Safety Issue?: Yes

Secondary Measures

• Disabling stroke
  • Time Frame: during the follow-up
    Safety Issue?: Yes
• Ischemic stroke
  • Time Frame: during the follow-up
    Safety Issue?: Yes
• Cerebral haemorrhage
  • Time Frame: during the follow-up
    Safety Issue?: Yes
• Ischemic stroke, TIA, or systemic embolism
  • Time Frame: during the follow-up
    Safety Issue?: Yes
• Death (all causes)
  • Time Frame: during the follow-up
    Safety Issue?: Yes
• Vascular death
  • Time Frame: during the follow-up
    Safety Issue?: Yes
• Moderate to severe bleeding complications
  • Time Frame: during the follow-up
    Safety Issue?: Yes
• Procedural or device complications
  • Time Frame: within 30 days
    Safety Issue?: Yes

Inclusion Criteria:

• Male or female, 16 <= age <= 60 ans.
• Recent (<= 6 months) ischemic stroke documented by CT-san or MRI (whatever the duration of symptoms: shorter or longer than 24 hours).
• Modified Rankin score <=3.
• Absence of any other identifiable cause of stroke
• Presence of a PFO with at least one of the following characteristics:
• right-to-left shunt > 30 microbubbles, at rest or during provocative manoeuvres, by TTE ou TOE
• associated ASA (base ≥ à 15 mm, total excursion > à 10 mm) by TOE
• Informed consent.

Exclusion Criteria:

• Any identifiable cause of ischemic stroke other than PFO.
• Isolated atrial septal defect or atrial septal defect associated with PFO with significant left-to-right shunt requiring closure.
• Previous surgical or endovascular treatments of PFO or ASA.
• Known or suspected pregnancy (beta hCG test must be performed before inclusion).
• Women who are breast-feeding.
• Inability to comply with the treatments or follow-up requirements of the study.
• No affiliation to the national health service.
• Presence of other medical problems that would either lead to inability to complete the trial or interfere with the assessment of outcomes.
• Participation in another study.
• Unable to understand the full meaning of the informed consent.
• Related medical treatments of the trial:
• Long-term oral anticoagulation or antiplatelet therapy is indicated for another disease.
• Contra-indication to antiplatelet therapy or oral anticoagulants :
• 3-arm trial : contra-indication to aspirin or clopidogrel or antivitamins K
• 2-arm trial (closure vs antiplatelet therapy) : contra-indication to aspirin or clopidogrel
• 2-arm trial (antivitamins K vs antiplatelet therapy : contra-indication to antivitamins K or to any antiplatelet drug
• Increased risk of bleeding, such as severe hepatic insufficiency, current peptic ulceration, proliferative diabetic retinopathy, history of severe systemic bleeding (e.g. gastrointestinal bleeding, gross hematuria, intraocular bleeding, hemorrhagic stroke, or intracranial hemorrhage), or other history of bleeding diathesis or coagulopathy.
• Related to endovascular treatments :
• Infection requiring antibiotics (inclusion is possible after healing, 4 weeks after withdrawal of antibiotics).
• Very large or multi-perforated ASA for which endovascular treatments is deemed too risky.
• Presence of thrombus or occlusion between the venous access and the right atrium.
• Presence of an inferior vena cava filter.
• Severe pulmonary hypertension.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 16 Years

Maximum Age for this Clinical Trial: 60 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Overall Clinical Trial Officials and Contacts

MAS Jean-Louis, MD, PhD Principal Investigator Centre hospitalier sainte Anne  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00562289

Study ID Number: P060406

ClinicalTrials.gov Identifier: NCT00562289

Health Authority: France: Ministry of Health