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Patent Foramen Ovale Closure or Anticoagulants Versus Antiplatelet Therapy to Prevent Stroke Recurrence

Phase 3
Completed
Conditions
Ischemic Stroke
Patent Foramen Ovale
Atrial Septal Aneurysm
Migraine
Interventions
Drug: Antivitamins K or rivaroxaban or dabigatran or apixaban
Device: Devices for PFO closure
Registration Number
NCT00562289
Lead Sponsor
Assistance Publique - Hôpitaux de Paris
Brief Summary

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.

Detailed Description

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
664
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
aspirinaspirinaspirin use like antiplatelet
anticoagulantAntivitamins K or rivaroxaban or dabigatran or apixabanAntivitamins K or rivaroxaban or dabigatran or apixaban
Devices for PFO closureDevices for PFO closureDevices for PFO closure
Primary Outcome Measures
NameTimeMethod
stroke(fatal or not)during the follow up (between 2 or 9 years)
Secondary Outcome Measures
NameTimeMethod
Ischemic strokeduring the follow-up
Cerebral haemorrhageduring the follow-up
Ischemic stroke, TIA, or systemic embolismduring the follow-up
Death (all causes)during the follow-up
Disabling strokeduring the follow-up
Vascular deathduring the follow-up
Moderate to severe bleeding complicationsduring the follow-up
Procedural or device complicationswithin 30 days

Trial Locations

Locations (1)

Hôpital Saint-Anne

🇫🇷

Paris, France

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