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

NCT ID: NCT00562289

Last Updated: 2017-10-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

664 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-12-31

Study Completion Date

2016-12-31

Brief Summary

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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

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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

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Ischemic Stroke Patent Foramen Ovale Atrial Septal Aneurysm Migraine

Keywords

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Stroke Patent Foramen Ovale Atrial septal aneurysm Antiplatelet therapy Oral anticoagulants Transcatheter closure Migraine

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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aspirin

aspirin use like antiplatelet

Group Type ACTIVE_COMPARATOR

aspirin

Intervention Type DRUG

during the follow up

anticoagulant

Antivitamins K or rivaroxaban or dabigatran or apixaban

Group Type EXPERIMENTAL

Antivitamins K or rivaroxaban or dabigatran or apixaban

Intervention Type DRUG

during the follow up

Devices for PFO closure

Devices for PFO closure

Group Type EXPERIMENTAL

Devices for PFO closure

Intervention Type DEVICE

endovascular treatment no longer than 21 days after the random.

Interventions

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aspirin

during the follow up

Intervention Type DRUG

Antivitamins K or rivaroxaban or dabigatran or apixaban

during the follow up

Intervention Type DRUG

Devices for PFO closure

endovascular treatment no longer than 21 days after the random.

Intervention Type DEVICE

Other Intervention Names

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clopidogrel combination aspirin-dipyridamole Each device for PFO closure must have the CE mark and be approved by the Interventional Cardiology Committee

Eligibility Criteria

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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.
Minimum Eligible Age

16 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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MAS Jean-Louis, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Centre hospitalier sainte Anne

Locations

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Hôpital Saint-Anne

Paris, , France

Site Status

Countries

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France

References

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Mas JL, Derumeaux G, Guillon B, Massardier E, Hosseini H, Mechtouff L, Arquizan C, Bejot Y, Vuillier F, Detante O, Guidoux C, Canaple S, Vaduva C, Dequatre-Ponchelle N, Sibon I, Garnier P, Ferrier A, Timsit S, Robinet-Borgomano E, Sablot D, Lacour JC, Zuber M, Favrole P, Pinel JF, Apoil M, Reiner P, Lefebvre C, Guerin P, Piot C, Rossi R, Dubois-Rande JL, Eicher JC, Meneveau N, Lusson JR, Bertrand B, Schleich JM, Godart F, Thambo JB, Leborgne L, Michel P, Pierard L, Turc G, Barthelet M, Charles-Nelson A, Weimar C, Moulin T, Juliard JM, Chatellier G; CLOSE Investigators. Patent Foramen Ovale Closure or Anticoagulation vs. Antiplatelets after Stroke. N Engl J Med. 2017 Sep 14;377(11):1011-1021. doi: 10.1056/NEJMoa1705915.

Reference Type RESULT
PMID: 28902593 (View on PubMed)

Turc G, Lee JY, Brochet E, Kim JS, Song JK, Mas JL; CLOSE and DEFENSE-PFO Trial Investigators. Atrial Septal Aneurysm, Shunt Size, and Recurrent Stroke Risk in Patients With Patent Foramen Ovale. J Am Coll Cardiol. 2020 May 12;75(18):2312-2320. doi: 10.1016/j.jacc.2020.02.068.

Reference Type DERIVED
PMID: 32381162 (View on PubMed)

Turc G, Calvet D, Guerin P, Sroussi M, Chatellier G, Mas JL; CLOSE Investigators. Closure, Anticoagulation, or Antiplatelet Therapy for Cryptogenic Stroke With Patent Foramen Ovale: Systematic Review of Randomized Trials, Sequential Meta-Analysis, and New Insights From the CLOSE Study. J Am Heart Assoc. 2018 Jun 17;7(12):e008356. doi: 10.1161/JAHA.117.008356.

Reference Type DERIVED
PMID: 29910193 (View on PubMed)

Mas JL, Derumeaux G, Amarenco P, Arquizan C, Aubry P, Barthelet M, Bertrand B, Brochet E, Cabanes L, Donal E, Dubois-Rande JL, Durand-Zaleski I, Ernande L, Finet G, Fraisse A, Giroud M, Guerin P, Habib G, Juliard JM, Leys D, Lievre M, Lusson JR, Marcon F, Michel P, Moulin T, Mounier-Vehier F, Pierard L, Piot C, Rey C, Rodier G, Roudaut R, Schleich JM, Teiger E, Turc G, Vuillier F, Weimar C, Woimant F, Chatellier G; CLOSE investigators. close: Closure of patent foramen ovale, oral anticoagulants or antiplatelet therapy to prevent stroke recurrence: Study design. Int J Stroke. 2016 Aug;11(6):724-32. doi: 10.1177/1747493016643551. Epub 2016 Apr 7.

Reference Type DERIVED
PMID: 27056964 (View on PubMed)

Other Identifiers

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P060406

Identifier Type: -

Identifier Source: org_study_id