Clinical trial NCT05387954: PFO Closure, Oral Anticoagulants or Antiplatelet Therapy After PFO-associated Stroke in Patients Aged 60 to 80 Years
Official title: Transcatheter Patent Foramen Ovale (PFO) Closure, Oral Anticoagulants or Antiplatelet Therapy After PFO-associated Stroke in Patients Between 60 and 80 Years Old : a Randomised Controlled Trial.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
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
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: Ministry of Health, France
name: W.L.Gore & Associates
name: Abbott
name: Occlutech International AB
name: Centre Hospitalier St Anne
First posted: 2022-05-24
Enrollment: 792
Sex: ALL
Minimum age (years): 60
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: PFO closure + antiplatelet therapy versus antiplatelet therapy alone Oral anticoagulants versus antiplatelet therapy
Primary purpose: PREVENTION

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.

Detailed description: The CLOSE trial (NCT00562289, NEJM 2017) has unambiguously demonstrated the superiority of patent foramen ovale (PFO) closure over antiplatelet therapy alone in patients aged up to 60 years with a PFO associated with an atrial septal aneurysm (ASA) or a large right-to-left shunt (so-called "high-risk PFO"), and an otherwise unexplained ischemic stroke. Oral anticoagulant therapy is also a logical approach assuming that PFO-related strokes are due to paradoxical embolism which implies a venous source of embolism, or to direct embolization of a thrombus formed at the atrial level. The CLOSE trial also suggested that oral anticoagulants might reduce stroke recurrence compared to aspirin.

There is accumulating evidence that presence of a PFO is significantly associated with cryptogenic stroke in patients over 60 years. Cryptogenic ischemic strokes represent about one third of all ischemic strokes in patients older than 60 years. However, the optimal therapeutic strategy in patients older than 60 years with a PFO and an otherwise unexplained ischemic stroke is unknown, because these patients were excluded from randomized trials.

The hypothesis tested in this trial is that transcatheter PFO closure plus long-term antiplatelet therapy is superior to antiplatelet therapy alone and that oral anticoagulant therapy is superior to antiplatelet therapy to prevent recurrent stroke in patients aged 60 to 80 years who have a high-risk PFO and a recent otherwise unexplained ischemic stroke.

Eligibility criteria: Inclusion Criteria:

* 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 opacification of the right atrium, detected 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 with ASA on transoesophageal echocardiography: excursion \>10 mm
* Affiliation to a French Health Insurance system. Informed consent.

Exclusion Criteria:

* 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.
* Patient unable to understand the informed consent form. Patient under tutorship, curatorship, or legal protection.

Primary outcomes:
measure: Time to recurrent stroke (ischemic or hemorrhagic fatal or non-fatal)
timeFrame: 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:
measure: Time to disabling stroke
timeFrame: 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)
measure: Time to ischemic stroke
timeFrame: 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)
measure: Time to ischemic stroke or systemic embolism
timeFrame: 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)
measure: Time to transient ischemic attack,
timeFrame: 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)
measure: Time to vascular death
timeFrame: 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)
measure: Time to all-cause mortality
timeFrame: From date of randomization until the date of death, assessed from up to 4 years (for the last patient included) to up to 8 years (for the first patient included)
measure: Quality of life score
timeFrame: Every 6 months after randomization or up to 4 years (for the last patient included) to up to 8 years (for the first patient included)]
measure: Time to fatal, life-threatening or major hemorrhage, including intracerebral and Intracranial hemorrhage
timeFrame: From date of randomization until the date of first fatal,life-threatening or major hemorrhage,including intracerebral and Intracranial hemorrhage,assessed from up to 4 years(for the last patient included) to up to 8 years(for the first patient included)
measure: Proportion of success of device implantation, of the procedure and of PFO closure,
timeFrame: 6 months after PFO closure
measure: Time to ischemic stroke recurrence according to the presence of a residual shunt
timeFrame: From date of PFO closure until the date of first ischemic stroke recurrence, assessed from up to 4 years (for the last patient included) to up to 8 years (for the first patient included), according to the presence of residual shunt]
measure: Time to new-onset atrial fibrillation
timeFrame: From date of randomization until the date of new-onset atrial fibrillation, assessed from up to 4 years (for the last patient included) to up to 8 years (for the first patient included)]
measure: Proportion of fatal, life-threatening or major procedure- or device-related complications
timeFrame: Within 4 weeks following the procedure (PFO closure)
measure: Costs
timeFrame: Within 48 months after randomization
measure: Incremental cost-utility ratio at 4 years (ICUR)
timeFrame: Within 48 months after randomization
Other outcomes:
Locations:
city: Amiens
country: France
facility: CHU Amiens
city: Arras
country: France
facility: CH Arras
city: Besançon
country: France
facility: CHU Jean Minjoz
city: Bordeaux
country: France
facility: CHU Bordeaux - GH Pellegrin
city: Brest
country: France
facility: CHRU La Cavale Blanche
city: Bron
country: France
facility: HCL-Groupement Hospitalier Lyon Est
city: Caen
country: France
facility: CHU Côte de Nacre
city: Clermont-Ferrand
country: France
facility: CHU Clermont Ferrand
city: Corbeil-Essonnes
country: France
facility: CH Sud Francilien
city: Créteil
country: France
facility: Hôpital Henri Mondor
city: Dijon
country: France
facility: CHU Dijon-Hôpital François Mitterrand
city: Grenoble
country: France
facility: CH Grenoble-Site Nord
city: La Rochelle
country: France
facility: GPE Hospitalier La Rochelle-Ré-Aunis
city: Le Chesnay
country: France
facility: CH Versailles-Hôpital Mignot
city: Le Kremlin-Bicetre
country: France
facility: CHU Bicêtre
city: Lille
country: France
facility: CHRU Lille-Hôpital Salengro
city: Marseille
country: France
facility: Hôpital de la Timone
city: Meaux
country: France
facility: Grand Hôpital de l'Est Francilien
city: Montpellier
country: France
facility: Hôpital Gui de Chauliac
city: Nancy
country: France
facility: CHRU Nancy-Hôpital central
city: Nice
country: France
facility: CHU de Nice-Hôpital Pasteur
city: Nîmes
country: France
facility: CHU Carémeau
city: Orsay
country: France
facility: CH Orsay
city: Paris
country: France
facility: APHP Hôpital Lariboisière
city: Paris
country: France
facility: Hôpital Pitié Salpêtrière
city: Paris
country: France
facility: GHU Paris Psychiatrie et Neurosciences
city: Paris
country: France
facility: Groupe Hospitalier Paris Saint-Joseph
city: Paris
country: France
facility: APHP Hôpital Bichat
city: Paris
country: France
facility: Fondation Adolphe de Rothschild
city: Perpignan
country: France
facility: CH Perpignan
city: Poitiers
country: France
facility: CHU La Milétrie
city: Pontoise
country: France
facility: Hôpital Novo
city: Rennes
country: France
facility: CHU Rennes-Hôpital Pontchaillou
city: Rouen
country: France
facility: CHU Rouen-Hôpital Charles-Nicolle
city: Saint Brieuc
country: France
facility: CH Yves Le Foll
city: Saint Herblain
country: France
facility: CHU Nantes-Hôpital Nord Laennec
city: Saint-Priest en Jarez
country: France
facility: CHU Saint-Etienne-Hôpital Nord
city: Strasbourg
country: France
facility: Hôpital Hautepierre
city: Suresnes
country: France
facility: Hôpital Foch
city: Toulouse
country: France
facility: CHU Toulouse-Hôpital Pierre Paul Riquet
city: Tours
country: France
facility: CHRU Tours- Hôpital Bretonneau
Study officials:
affiliation: GHU Psychiatrie et Neurosciences Paris
name: Jean-Louis Mas, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hôpital Européen Georges-Pompidou
name: Gilles Chatellier, MD
role: STUDY_DIRECTOR
References: