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

Assistance Publique - Hôpitaux de Paris

Status and phase: Completed; Phase 3

Conditions: Ischemic Stroke; Atrial Septal Aneurysm; Migraine; Patent Foramen Ovale

Treatments: Drug: aspirin; Device: Devices for PFO closure; Drug: Antivitamins K or rivaroxaban or dabigatran or apixaban

Study type: Interventional

Funder types: Other

Identifiers

NCT00562289

P060406

Details and patient eligibility

About

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.

Full 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.

Enrollment: 664 patients

Sex: All

Ages: 16 to 60 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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664 participants in 3 patient groups

aspirin

Active Comparator group

Description:

aspirin use like antiplatelet

Treatment:

Drug: aspirin

anticoagulant

Experimental group

Description:

Antivitamins K or rivaroxaban or dabigatran or apixaban

Treatment:

Drug: Antivitamins K or rivaroxaban or dabigatran or apixaban

Devices for PFO closure

Experimental group

Description:

Devices for PFO closure

Treatment:

Device: Devices for PFO closure