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

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2007 by Assistance Publique - Hôpitaux de Paris
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT00562289
First received: November 21, 2007
Last updated: September 17, 2013
Last verified: November 2007
  Purpose

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.


Condition Intervention Phase
Ischemic Stroke
Patent Foramen Ovale
Atrial Septal Aneurysm
Migraine
Drug: aspirin
Drug: Antivitamins K
Device: Devices for PFO closure
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Closure of Patent Foramen Ovale or Anticoagulants Versus Antiplatelet Therapy to Prevent Stroke Recurrence

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • stroke(fatal or not) [ Time Frame: during the follow up (between 3 or 5 years) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Disabling stroke [ Time Frame: during the follow-up ] [ Designated as safety issue: Yes ]
  • Ischemic stroke [ Time Frame: during the follow-up ] [ Designated as safety issue: Yes ]
  • Cerebral haemorrhage [ Time Frame: during the follow-up ] [ Designated as safety issue: Yes ]
  • Ischemic stroke, TIA, or systemic embolism [ Time Frame: during the follow-up ] [ Designated as safety issue: Yes ]
  • Death (all causes) [ Time Frame: during the follow-up ] [ Designated as safety issue: Yes ]
  • Vascular death [ Time Frame: during the follow-up ] [ Designated as safety issue: Yes ]
  • Moderate to severe bleeding complications [ Time Frame: during the follow-up ] [ Designated as safety issue: Yes ]
  • Procedural or device complications [ Time Frame: within 30 days ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 900
Study Start Date: December 2007
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: aspirin
aspirin use like antiplatelet
Drug: aspirin
during the follow up
Other Names:
  • aspirin
  • clopidogrel
  • combination aspirin-dipyridamole
Experimental: anticoagulant
Antivitamins K or rivaroxaban or dabigatran
Drug: Antivitamins K
during the follow up
Other Name: Antivitamins K
Experimental: Devices for PFO closure
Devices for PFO closure
Device: Devices for PFO closure
endovascular treatment no longer than 21 days after the random.
Other Names:
  • Each device for PFO closure must have the CE mark
  • and be approved by the Interventional Cardiology Committee

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.
  Eligibility

Ages Eligible for Study:   16 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00562289

Locations
France
Hôpital Saint-Anne Recruiting
Paris, France
Contact: Jean-Louis MAS    +33145658284    jl.mas@ch-sainte-anne.fr   
Principal Investigator: Jean Louis MAS         
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Principal Investigator: MAS Jean-Louis, MD, PhD Centre hospitalier sainte Anne
  More Information

No publications provided

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT00562289     History of Changes
Other Study ID Numbers: P060406
Study First Received: November 21, 2007
Last Updated: September 17, 2013
Health Authority: France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Stroke
Patent Foramen Ovale
Atrial septal aneurysm
Antiplatelet therapy
Oral anticoagulants
Transcatheter closure
Migraine

Additional relevant MeSH terms:
Anticoagulants
Aneurysm
Foramen Ovale, Patent
Recurrence
Stroke
Cerebral Infarction
Migraine Disorders
Vascular Diseases
Cardiovascular Diseases
Heart Septal Defects, Atrial
Heart Septal Defects
Heart Defects, Congenital
Cardiovascular Abnormalities
Heart Diseases
Congenital Abnormalities
Disease Attributes
Pathologic Processes
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Brain Infarction
Brain Ischemia
Headache Disorders, Primary
Headache Disorders
Aspirin
Aspirin, dipyridamole drug combination
Dipyridamole
4-Hydroxycoumarins
Vitamin K

ClinicalTrials.gov processed this record on July 28, 2014