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

October 18, 2017 updated by: Assistance Publique - Hôpitaux de Paris

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 Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

664

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Paris, France
        • Hôpital Saint-Anne

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 60 years (ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: aspirin
aspirin use like antiplatelet
Drug: aspirin
during the follow up
Other Names:
  • clopidogrel
  • combination aspirin-dipyridamole
EXPERIMENTAL: anticoagulant
Antivitamins K or rivaroxaban or dabigatran or apixaban
Drug: Antivitamins K or rivaroxaban or dabigatran or apixaban
during the follow up
EXPERIMENTAL: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
stroke(fatal or not)
Time Frame: during the follow up (between 2 or 9 years)
during the follow up (between 2 or 9 years)

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assistance Publique - Hôpitaux de Paris

Investigators

  • Principal Investigator: MAS Jean-Louis, MD, PhD, Centre hospitalier Sainte Anne

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2007

Primary Completion (ACTUAL)

December 1, 2016

Study Completion (ACTUAL)

December 1, 2016

Study Registration Dates

First Submitted

November 21, 2007

First Submitted That Met QC Criteria

November 21, 2007

First Posted (ESTIMATE)

November 22, 2007

Study Record Updates

Last Update Posted (ACTUAL)

October 19, 2017

Last Update Submitted That Met QC Criteria

October 18, 2017

Last Verified

January 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P060406

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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