NCT00562289

Brief Summary

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
664

participants targeted

Target at P75+ for phase_3

Timeline
Completed

Started Dec 2007

Longer than P75 for phase_3

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 21, 2007

Completed
1 day until next milestone

First Posted

Study publicly available on registry

November 22, 2007

Completed
9 days until next milestone

Study Start

First participant enrolled

December 1, 2007

Completed
9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2016

Completed
Last Updated

October 19, 2017

Status Verified

January 1, 2017

Enrollment Period

9 years

First QC Date

November 21, 2007

Last Update Submit

October 18, 2017

Conditions

Ischemic StrokePatent Foramen OvaleAtrial Septal AneurysmMigraine

Keywords

StrokePatent Foramen OvaleAtrial septal aneurysmAntiplatelet therapyOral anticoagulantsTranscatheter closureMigraine

Outcome Measures

Primary Outcomes (1)

  • stroke(fatal or not)

    during the follow up (between 2 or 9 years)

Secondary Outcomes (8)

  • Disabling stroke

    during the follow-up

  • Ischemic stroke

    during the follow-up

  • Cerebral haemorrhage

    during the follow-up

  • Ischemic stroke, TIA, or systemic embolism

    during the follow-up

  • Death (all causes)

    during the follow-up

  • +3 more secondary outcomes

Study Arms (3)

aspirin

ACTIVE COMPARATOR

aspirin use like antiplatelet

Drug: aspirin

anticoagulant

EXPERIMENTAL

Antivitamins K or rivaroxaban or dabigatran or apixaban

Drug: Antivitamins K or rivaroxaban or dabigatran or apixaban

Devices for PFO closure

EXPERIMENTAL

Devices for PFO closure

Device: Devices for PFO closure

Interventions

aspirinDRUG

during the follow up

Also known as: clopidogrel, combination aspirin-dipyridamole
aspirin
Antivitamins K or rivaroxaban or dabigatran or apixabanDRUG

during the follow up

anticoagulant
Devices for PFO closureDEVICE

endovascular treatment no longer than 21 days after the random.

Also known as: Each device for PFO closure must have the CE mark, and be approved by the Interventional Cardiology Committee
Devices for PFO closure

Eligibility Criteria

Age16 Years - 60 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.
  • 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 :
  • arm trial : contra-indication to aspirin or clopidogrel or antivitamins K
  • arm trial (closure vs antiplatelet therapy) : contra-indication to aspirin or clopidogrel
  • arm trial (antivitamins K vs antiplatelet therapy : contra-indication to antivitamins K or to any antiplatelet drug
  • +6 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Hôpital Saint-Anne

Paris, France

Location

Related Publications (4)

  • 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.

    PMID: 28902593RESULT

  • 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.

    PMID: 32381162DERIVED

  • 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.

    PMID: 29910193DERIVED

  • 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.

    PMID: 27056964DERIVED

MeSH Terms

Conditions

Ischemic StrokeForamen Ovale, PatentMigraine DisordersStroke

Interventions

AspirinClopidogrelAspirin, Dipyridamole Drug Combinationantivitamins KRivaroxabanDabigatranapixabanEquipment and Supplies

Condition Hierarchy (Ancestors)

Cerebrovascular DisordersBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesVascular DiseasesCardiovascular DiseasesHeart Septal Defects, AtrialHeart Septal DefectsHeart Defects, CongenitalCardiovascular AbnormalitiesHeart DiseasesCongenital AbnormalitiesCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesHeadache Disorders, PrimaryHeadache Disorders

Intervention Hierarchy (Ancestors)

SalicylatesHydroxybenzoatesPhenolsBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsTiclopidineThienopyridinesThiophenesSulfur CompoundsPyridinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingDipyridamolePyrimidinesDrug CombinationsPharmaceutical PreparationsMorpholinesOxazinesBenzimidazoles

Study Officials

  • MAS Jean-Louis, MD, PhD

    Centre hospitalier sainte Anne

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 21, 2007

First Posted

November 22, 2007

Study Start

December 1, 2007

Primary Completion

December 1, 2016

Study Completion

December 1, 2016

Last Updated

October 19, 2017

Record last verified: 2017-01

Locations

FR(1)