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

Ischemic Stroke Clinical Trial

— CLOSE  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00562289
• Other study ID #: P060406
• Status: Completed
• Phase: Phase 3
• First received: November 21, 2007
• Last updated: October 18, 2017
• Start date: December 2007
• Est. completion date: December 2016

Study information

• Verified date: January 2017
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 664
• Est. completion date: December 2016
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

• Aneurysm
• Atrial Septal Aneurysm
• Foramen Ovale, Patent
• Ischemic Stroke
• Migraine
• Migraine Disorders
• Patent Foramen Ovale
• Recurrence
• Stroke

Intervention

Drug:
• aspirin
during the follow up
• Antivitamins K or rivaroxaban or dabigatran or apixaban
during the follow up

Device:
• Devices for PFO closure
endovascular treatment no longer than 21 days after the random.

Locations

Country	Name	City	State
France	Hôpital Saint-Anne	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

References & Publications (1)

Mas JL, Derumeaux G, Guillon B, Massardier E, Hosseini H, Mechtouff L, Arquizan C, Béjot 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, Zub — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	stroke(fatal or not)		during the follow up (between 2 or 9 years)
Secondary	Disabling stroke		during the follow-up
Secondary	Ischemic stroke		during the follow-up
Secondary	Cerebral haemorrhage		during the follow-up
Secondary	Ischemic stroke, TIA, or systemic embolism		during the follow-up
Secondary	Death (all causes)		during the follow-up
Secondary	Vascular death		during the follow-up
Secondary	Moderate to severe bleeding complications		during the follow-up
Secondary	Procedural or device complications		within 30 days