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

Completed

Phase 3 Results N/A

Trial Description

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.

Conditions

Interventions

  • Anticoagulants Drug
  • PFO Closure + chronic antiplatelet therapy Procedure/Surgery
    Intervention Desc: For the non-surgical closure of a patent foramen ovale (PFO) in patients with recurrent cryptogenic stroke due to presumed paradoxical embolism through a patent foramen ovale. Chronic antiplatelet therapy (ASA or clopidogrel or association of ASA & dipyridamole).
  • Chronic Antiplatelet Treatment Drug
    Intervention Desc: ASA or clopidogrel or association of ASA & dipyridamole
  • Aspirin Drug
    Other Names: clopidogrel; combination aspirin-dipyridamole
    Intervention Desc: during the follow up
    ARM 1: Kind: Experimental
    Label: 1
    ARM 2: Kind: Experimental
    Label: aspirin
    Description: aspirin use like antiplatelet
  • Antivitamins K Drug
    Other Names: Antivitamins K
    Intervention Desc: during the follow up
    ARM 1: Kind: Experimental
    Label: 2
    ARM 2: Kind: Experimental
    Label: anticoagulant
    Description: Antivitamins K or rivaroxaban or dabigatran
  • Devices for PFO closure Device
    Other Names: Each device for PFO closure must have the CE mark; and be approved by the Interventional Cardiology Committee
    Intervention Desc: endovascular treatment no longer than 21 days after the random.
    ARM 1: Kind: Experimental
    Label: 3
    ARM 2: Kind: Experimental
    Label: Devices for PFO closure
    Description: Devices for PFO closure
  • Antivitamins K or rivaroxaban or dabigatran or apixaban Drug
    Intervention Desc: during the follow up
    ARM 1: Kind: Experimental
    Label: anticoagulant
    Description: Antivitamins K or rivaroxaban or dabigatran or apixaban

Trial Design

  • Allocation: Randomized
  • Masking: Open Label
  • Purpose: Prevention
  • Endpoint: Safety/Efficacy Study
  • Intervention: Parallel Assignment

Patient Involvement

Patients will be randomized to either drug therapy or PFO closure +chronic antiplatelet therapy arm as treatment for PFO. Target INR range 2-3 for chronic oral anticoagulation arm.

Outcomes

Type Measure Time Frame Safety Issue
Primary Stroke (fatal or not) during the follow up of 3 or 5 years.
Secondary Disabling stroke; ischemic stroke; cerebral haemorrhage; ischemic stroke, TIA, or systemic embolism; mortality; vascular death; moderate to severe bleeding complications during the follow-up. Procedural or device complications within 30 days.
Primary stroke(fatal or not) during the follow up (between 3 or 5 years) Yes
Secondary Disabling stroke during the follow-up Yes
Secondary Ischemic stroke during the follow-up Yes
Secondary Cerebral haemorrhage during the follow-up Yes
Secondary Ischemic stroke, TIA, or systemic embolism during the follow-up Yes
Secondary Death (all causes) during the follow-up Yes
Secondary Vascular death during the follow-up Yes
Secondary Moderate to severe bleeding complications during the follow-up Yes
Secondary Procedural or device complications within 30 days Yes

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