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Ischemic StrokePhase 3CLOSENCT00562289

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

A Phase 3 study testing aspirin, Antivitamins K or rivaroxaban or dabigatran or apixaban and Devices for PFO closure in people with Ischemic Stroke and Patent Foramen Ovale, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 16 to 60 years
What is being tested?
aspirin, Antivitamins K or rivaroxaban or dabigatran or apixaban and Devices for PFO closure
Type of treatment
Medical device
Could I receive a placebo?
No, everyone receives an active treatment
How many people
664 participants
Where
1 siteFrance
Study dates
Dec 2007to Dec 2016
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 16 to 60 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 23Show fewer
  • 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.

Trial locations and contacts

1 site in 1 country.

France1 site

  • Hôpital Saint-Anne

    Paris

Other trials in France

About this study

Official title: 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.

Read the 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.
Being tested
aspirin, Antivitamins K or rivaroxaban or dabigatran or apixaban, Devices for PFO closure
Keywords
Stroke, Patent Foramen Ovale, Atrial septal aneurysm, Antiplatelet therapy, Oral anticoagulants, Transcatheter closure, Migraine
Medical subject headings
Ischemic Stroke, Foramen Ovale, Patent, Migraine Disorders, Stroke

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • aspirinDrug

    Also called clopidogrel, combination aspirin-dipyridamole

    during the follow up

  • Antivitamins K or rivaroxaban or dabigatran or apixabanDrug

    during the follow up

  • Devices for PFO closureDevice

    Also called Each device for PFO closure must have the CE mark, and be approved by the Interventional Cardiology Committee

    endovascular treatment no longer than 21 days after the random.

Study groups in NCT00562289
Study groupRoleWhat they receive
aspirinActive comparatoraspirin use like antiplatelet
Receives: Drug: aspirin
anticoagulantExperimentalAntivitamins K or rivaroxaban or dabigatran or apixaban
Receives: Drug: Antivitamins K or rivaroxaban or dabigatran or apixaban
Devices for PFO closureExperimentalDevices for PFO closure
Receives: Device: Devices for PFO closure

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. stroke(fatal or not)

    Measured: during the follow up (between 2 or 9 years)

Secondary outcomes (8)

  1. Disabling stroke

    Measured: during the follow-up

  2. Ischemic stroke

    Measured: during the follow-up

  3. Cerebral haemorrhage

    Measured: during the follow-up

  4. Ischemic stroke, TIA, or systemic embolism

    Measured: during the follow-up

  5. Death (all causes)

    Measured: during the follow-up

  6. Vascular death

    Measured: during the follow-up

  7. Moderate to severe bleeding complications

    Measured: during the follow-up

  8. Procedural or device complications

    Measured: within 30 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Nov 2007 (estimated)
  2. Study startDec 2007
  3. Primary completionDec 2016
  4. Study completionDec 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
664 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00562289
Sponsor's protocol ID
P060406
Acronym
CLOSE
Status last verified
Jan 2017
First submitted
21 Nov 2007
Last updated
19 Oct 2017
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 28902593

  • 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.

    PubMed 32381162

  • 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.

    PubMed 29910193

  • 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.

    PubMed 27056964

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing aspirin, Antivitamins K or rivaroxaban or dabigatran or apixaban and Devices for PFO closure in people with Ischemic Stroke and Patent Foramen Ovale, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

stroke(fatal or not) (time frame: during the follow up (between 2 or 9 years)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00562289, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Oct 2017.

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