PFO Closure, Oral Anticoagulants or Antiplatelet Therapy After PFO-associated Stroke in Patients Aged 60 to 80 Years

NCT05387954 | Recruiting Phase 3 DMC

• 3 other identifiers: APHP2110412021-A03197-34PHRC-20-0680
• Study Type: interventional
• Target: 792
• Locations: 1 country
• Sites: 42

Brief Summary

To assess whether PFO closure plus antiplatelet therapy is superior to antiplatelet therapy alone and whether oral anticoagulant therapy is superior to antiplatelet therapy to prevent stroke recurrence in patients aged 60 to 80 years with a PFO with large shunt (\> 20 microbubbles) or a PFO associated with an ASA (\> 10 mm), and an otherwise unexplained ischemic stroke.

Conditions

Cryptogenic Ischemic Stroke; Patent Foramen Ovale

Keywords

Ischemic stroke; Cryptogenic stroke; Patent foramen ovale; Atrial septal aneurysm; Transcatheter PFO closure; Oral anticoagulants; Antiplatelet therapy; Randomized clinical tria

Outcome Measures

Primary Outcomes (1)

• Time to recurrent stroke (ischemic or hemorrhagic fatal or non-fatal)

  Stroke: sudden onset of focal neurological symptoms related to a disturbance of the cerebral circulation. Ischemic stroke : at least one of the following criteria: * Sudden onset of focal neurological symptoms with the presence of cerebral infarction in the appropriate territory on brain imaging (CT or MRI), regardless of the duration of symptoms (less than or more than 24 hours). * Sudden onset of focal neurological symptoms lasting more than 24 hours, with no apparent cause other than cerebral ischemia. Intracerebral hemorrhage: sudden onset of focal neurological symptoms with the presence of cerebral hemorrhage in the appropriate territory on brain imaging (CT or MRI), regardless of the duration of symptoms (less than or more than 24 hours) and regardless of the cause of the hemorrhage (spontaneous or secondary to trauma, tumour or another cause). Unknown type of stroke : the type of stroke cannot be determined with certainty and the symptoms last more than 24 hours.

  From date of randomization until the date of first recurrent stroke, assessed from up to 4 years (for the last patient included) to up to 8 years (for the first patient included)

Secondary Outcomes (14)

• Time to disabling stroke

  From date of randomization until the date of first recurrent disabling stroke, assessed from up to 4 years (for the last patient included) to up to 8 years (for the first patient included)

• Time to ischemic stroke

  From date of randomization until the date of first recurrent ischemic stroke, assessed from up to 4 years (for the last patient included) to up to 8 years (for the first patient included)

• Time to ischemic stroke or systemic embolism

  From date of randomization until the date of first recurrent ischemic stroke or systemic embolism, assessed from up to 4 years (for the last patient included) to up to 8 years (for the first patient included)

• Time to transient ischemic attack,

  From date of randomization until the date of first transient ischemic attack, assessed from up to 4 years (for the last patient included) to up to 8 years (for the first patient included)

• Time to vascular death

  From date of randomization until the date of vascular death, assessed from up to 4 years (for the last patient included) to up to 8 years (for the first patient included)

Study Arms (3)

Antiplatelet therapy

ACTIVE COMPARATOR

Aspirin OR clopidogrel

Drug: Antiplatelet therapy

Oral anticoagulants, Direct-Acting

EXPERIMENTAL

Apixaban (5mg twice a day) OR Dabigatran (150 mg twice a day) OR Rivaroxaban (20 mg once a day)

Drug: Oral Anticoagulant, Direct-Acting

PFO closure

EXPERIMENTAL

PFO closure followed by dual antiplatelet therapy (aspirin 75 mg/d + clopidogrel 75 mg/d) for 3 months, then by single antiplatelet therapy by aspirin or clopidogrel

Procedure: Transcatheter PFO closure; Drug: Antiplatelet therapy

Interventions

Antiplatelet therapy DRUG

Patients randomized to this arm will receive antiplatelet therapy throughout the study : aspirin 75 mg/d + clopidogrel 75 mg/d) for 3 months, then single antiplatelet therapy by aspirin or clopidogrel

Antiplatelet therapy; PFO closure

Transcatheter PFO closure PROCEDURE

PFO closure followed by dual antiplatelet therapy (aspirin 75 mg/d + clopidogrel 75 mg/d) for 3 months, then by single antiplatelet therapy by aspirin or clopidogrel until the end of the study.

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

PFO closure

Oral Anticoagulant, Direct-Acting DRUG

Apixaban (5mg twice a day) OR Dabigatran (150 mg twice a day) OR Rivaroxaban (20 mg once a day)

Oral anticoagulants, Direct-Acting

Eligibility Criteria

• Age: 60 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Man or woman aged 60 to 80 years.
• Recent (≤ 6 months) ischemic stroke confirmed by cerebral imaging regardless of symptom duration.
• Absence of a more probable cause of stroke than PFO after a standardized etiological work-up (see addenda).
• Presence of a PFO with at least 1 of the 2 following characteristics:
• PFO with large shunt (\> 20 microbubbles) appearing in the left atrium during at least one of the 3 cardiac cycles after complete opacification of the right atrium, detected either spontaneously or during provocative manoeuvers, on contrast transthoracic (TTE) or transoesophageal (TOE) echocardiography. The diagnosis of PFO by contrast TEE must be confirmed by contrast TOE showing a right-to-left passage of the contrast material across the PFO.
• PFO associated with an ASA on transoesophageal echocardiography: excursion \>10 mm
• Affiliation to a French Health Insurance system. Informed consent.

You may not qualify if:

• Life expectancy \< 4 years.
• Contraindication to both experimental treatments (PFO closure, oral anticoagulant therapy) or to the reference treatment (antiplatelet therapy) (see paragraph 20.5).
• Indication to long-term anticoagulant therapy.
• mRS \> 3.
• Presence of other medical conditions that would lead to inability to complete the study or interfere with the assessment of outcomes.
• Previous surgical or transcatheter treatment of PFO or ASA. Expected impossible follow-up or poor compliance.
• PFO associated with an atrial septal defect (ASD) requiring closure (significant shunt with impact on the right cavities, elevation of pulmonary pressures or QP/QS\>2)
• Patient unable to understand the informed consent form. Patient under tutorship, curatorship, or legal protection.

Sponsors & Collaborators

• Abbott: collaborator
• Assistance Publique - Hôpitaux de Paris: lead
• Ministry of Health, France: collaborator
• W.L.Gore & Associates: collaborator
• Occlutech International AB: collaborator
• Centre Hospitalier St Anne: collaborator

Study Sites (42)

CHU Amiens

Amiens, 80054, France

RECRUITING

Centre Hospitalier de la Côte Basque

Bayonne, 64100, France

RECRUITING

CHU Jean Minjoz

Besançon, 25000, France

RECRUITING

CHU Bordeaux - GH Pellegrin

Bordeaux, 33000, France

RECRUITING

CHRU La Cavale Blanche

Brest, 29200, France

RECRUITING

HCL-Groupement Hospitalier Lyon Est

Bron, 69677, France

RECRUITING

CHU Côte de Nacre

Caen, 14000, France

RECRUITING

CHU Clermont Ferrand

Clermont-Ferrand, 63000, France

RECRUITING

CH Sud Francilien

Corbeil-Essonnes, 91100, France

RECRUITING

Hôpital Henri Mondor

Créteil, 94010, France

RECRUITING

CHU Dijon-Hôpital François Mitterrand

Dijon, 21079, France

RECRUITING

Hôpital Raymond Poincaré

Garches, 92380, France

RECRUITING

CH Grenoble-Site Nord

Grenoble, 38043, France

RECRUITING

GPE Hospitalier La Rochelle-Ré-Aunis

La Rochelle, 17000, France

RECRUITING

CH Versailles-Hôpital Mignot

Le Chesnay, 78150, France

RECRUITING

CHU Bicêtre

Le Kremlin-Bicêtre, 94370, France

RECRUITING

CHRU Lille-Hôpital Salengro

Lille, 59037, France

RECRUITING

CHU Limoges - Site Dupuytren

Limoges, 87042, France

RECRUITING

Hôpital de la Timone

Marseille, 13005, France

RECRUITING

Grand Hôpital de l'Est Francilien

Meaux, 77140, France

RECRUITING

Hôpital Gui de Chauliac

Montpellier, 34295, France

RECRUITING

CHU de Nice-Hôpital Pasteur

Nice, 06000, France

RECRUITING

CHU Carémeau

Nîmes, 30900, France

RECRUITING

CH Orsay

Orsay, 91400, France

RECRUITING

APHP Hôpital Lariboisière

Paris, 75010, France

RECRUITING

Hôpital Pitié Salpêtrière

Paris, 75013, France

RECRUITING

GHU Paris Psychiatrie et Neurosciences

Paris, 75014, France

RECRUITING

Groupe Hospitalier Paris Saint-Joseph

Paris, 75014, France

RECRUITING

Fondation Adolphe de Rothschild

Paris, 75019, France

RECRUITING

CH Perpignan

Perpignan, 66000, France

RECRUITING

CHU La Milétrie

Poitiers, 86021, France

RECRUITING

Hôpital Novo

Pontoise, 95300, France

RECRUITING

CHU Rennes-Hôpital Pontchaillou

Rennes, 35000, France

RECRUITING

CHU Rouen-Hôpital Charles-Nicolle

Rouen, 76000, France

RECRUITING

CH Yves Le Foll

Saint-Brieuc, 22000, France

RECRUITING

CHU Nantes-Hôpital Nord Laennec

Saint-Herblain, 44093, France

RECRUITING

CHU Saint-Etienne-Hôpital Nord

Saint-Priest-en-Jarez, 42270, France

RECRUITING

Hôpital Hautepierre

Strasbourg, 67000, France

RECRUITING

Hôpital Foch

Suresnes, 92150, France

RECRUITING

CHU Toulouse-Hôpital Pierre Paul Riquet

Toulouse, 31059, France

RECRUITING

CHRU Tours- Hôpital Bretonneau

Tours, 37000, France

RECRUITING

Centre Hospitalier de Valenciennes

Valenciennes, 59300, France

RECRUITING

MeSH Terms

Conditions

Ischemic Stroke; Foramen Ovale, Patent

Interventions

Factor Xa Inhibitors

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Heart Septal Defects, Atrial; Heart Septal Defects; Heart Defects, Congenital; Cardiovascular Abnormalities; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Antithrombins; Serine Proteinase Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Anticoagulants; Hematologic Agents; Therapeutic Uses

Study Officials

• Jean-Louis Mas, MD

  GHU Psychiatrie et Neurosciences Paris

  PRINCIPAL INVESTIGATOR

• Gilles Chatellier, MD

  Hôpital Européen Georges-Pompidou

  STUDY DIRECTOR

Central Study Contacts

Carla Vandenabele

CONTACT

+331 44 84 57 27; carla.vandenabele@aphp.fr

Malha Berrah

CONTACT

malha.berrah@aphp.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The clinical event adjudication committee will blind to the treatment allocated by randomization.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: PFO closure + antiplatelet therapy versus antiplatelet therapy alone Oral anticoagulants versus antiplatelet therapy

Study Record Dates

• First Submitted: May 4, 2022
• First Posted: May 24, 2022
• Study Start: July 7, 2023
• Primary Completion (Estimated): July 7, 2031
• Study Completion (Estimated): July 7, 2031
• Last Updated: March 24, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Two years after the last publication
• Access Criteria: Data sharing must be accepted by the sponsor and the PI based on a scientific project and scientific involvement of the PI team. Collaboration will be fostered. Data sharing must respect the agreements made with funders. Teams wishing obtain IPD must meet the sponsor and PI team to present scientific (and commercial) purpose, IPD needed, format of data transmission, and timeframe. Technical feasability and financial support will be discussed before mandatory contractual agreement. Processing of shared data must comply with European General Data Protection Regulation (GDPR).

Locations

FR (42)