Comparación de Dos Dispositivos de Cierre de FOP en Adultos con Accidente Cerebrovascular Previo o AIT (SAFE-PFO)
Ensayo Controlado Aleatorizado que Compara la Seguridad y Eficacia del Dispositivo de Oclusión de FOP Cocoon Frente al Dispositivo de Cierre de FOP Amplatzer para el Cierre Percutáneo del Foramen Oval Permeable en Pacientes con Antecedentes de Accidente Cerebrovascular o Ataque Isquémico Transitorio: Un Ensayo sin Fines de Lucro, Simple Ciego e Impulsado por el Investigador
This study is a prospective, multicenter, randomized, controlled, single-blind, investigator-driven, non-profit clinical trial designed to compare the safety and efficacy of the Cocoon PFO Occluder with the Amplatzer PFO Occluder family in patients requiring percutaneous closure of a patent foramen ovale (PFO). Eligible participants are adults with a history of cryptogenic embolic stroke or neurologically confirmed transient ischemic attack (TIA) within the previous 12 months and a PFO suitable for transcatheter closure.
A total of up to 1260 subjects will be enrolled across multiple European centers. Participants will be randomly assigned in a 3:1 ratio to receive either the Cocoon PFO Occluder (experimental group) or an Amplatzer PFO closure device (control group). The procedure will be performed as soon as possible after randomization, preferably within 14 days and no later than 45 days.
The primary endpoint is a non-inferiority comparison of a composite outcome at 12 months, including recurrent ischemic stroke, TIA, or all-cause death. Secondary endpoints include PFO closure rate at 6 months, assessed by echocardiographic imaging, and other measures of safety, device performance, and clinical outcomes.
The study is conducted in a single-blind fashion: patients will not be informed of the device they receive unless they explicitly request this information. Any patient who chooses to be unblinded will continue to participate without affecting eligibility or follow-up, and the date of unblinding will be documented to allow appropriate sensitivity analyses.
This trial aims to provide robust comparative evidence on the clinical performance of the Cocoon PFO Occluder relative to the Amplatzer PFO Occluder to guide optimal device selection in patients with cryptogenic stroke or TIA associated with PFO.
Descripción general del estudio
Estado
Intervención / Tratamiento
Tipo de estudio
Inscripción (Estimado)
Fase
- No aplica
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Francesco Cardaioli, MD
- Número de teléfono: +39 338 1986562
- Correo electrónico: francesco.cardaioli@gmail.com
Copia de seguridad de contactos de estudio
- Nombre: Daniela Ramaccini, PhD, PharmaD
- Número de teléfono: +39 3534390426
- Correo electrónico: d.ramaccini@endocorelab.org
Ubicaciones de estudio
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North Rhine-Westphalia (Nordrhein-Westfalen)
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Bad Oeynhausen, North Rhine-Westphalia (Nordrhein-Westfalen), Alemania, 32545
- Reclutamiento
- Heart and Diabetes Center NRW (HDZ NRW), Clinic for General and Interventional Cardiology/Angiology
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Investigador principal:
- Werner Scholtz, MD
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Contacto:
- Werner Scholtz, MD
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
- Patients with >18 years of age and <65 years of age, regardless of gender
- Patients with normal or aneurysm type PFO confirmed by imaging examination [Transthoracic Echocardiography (TTE)/ Transesophageal Echocardiography (TOE) or Intracardiac Echocardiography], and who exhibit spontaneous right-to-left shunting or right-to-left shunting during Valsalva maneuver.
- Patients with history of cryptogenic embolic stroke or transient ischemic attack in the previous 12 months [stroke is defined as acute focal neurological deficit presumed to be due to focal ischemia, and either 1) symptoms persisting 24 hours or greater, or 2) symptoms persisting less than 24 hours but associated with MR or CT findings of a new, neuroanatomically relevant, cerebral infarct. Transient Ischemic Attack is defined as acute focal neurological deficit (defined as focal motor deficit, aphasia, difficulty walking, hemisensory deficit, amaurosis fugax, blindness, or focal visual deficit) presumed due to focal ischemia, lasting between 5 minutes and 24 hours, that is not associated with MR or CT findings of a new cerebral infarct]. The diagnosis of cryptogenic embolic stroke or TIA has to be confirmed by a neurologist.
- The size of PFO must be amenable to selection of a Cocoon PFO Occluder or Amplatzer PFO closure device.
- Patients are informed of the nature of the trial and agree to all requirements for participation in the trial, signed the informed consent form, and agreed to complete the follow-up and follow-up examination
Exclusion Criteria:
- Patients who have definite causes of stroke or transient ischemic attack unrelated to the PFO
- RLS caused by other causes, such as atrial septal defect or pulmonary arteriovenous shunt
- Patients with atrial fibrillation/atrial flutter (chronic or intermittent) Intracardiac thrombus or tumor
- Patients with mitral or aortic valve stenosis or severe regurgitation
- Mitral or aortic valve vegetation or prosthesis
- Active endocarditis or other untreated infectious diseases
- Dilated cardiomyopathy, hypertrophic cardiomyopathy, restrictive cardiomyopathy
- Left ventricular ejection fraction (LVEF) <35%
- Left ventricular aneurysm or akinesis Myocardial infarction or unstable angina pectoris within 12 months
- Previous intracardiac surgery or percutaneous PFO-closure
- Atherosclerosis or arteriopathy of intra- or extracranial vessels with >50% diameter stenosis in the artery supplying the infarcted territory.
- Patients with non-embolic cryptogenic stroke (for example lacunar stroke) or with other identifiable causes of stroke, including but not limited to aortic arch plaques (protruding >4 mm into the lumen), large artery atherosclerotic disease, an established cardioembolic source, small-vessel occlusive disease, or arterial dissection
- Glomerular filtration rate < 30 ml/min/1.73 m2 or with any history of renal dialysis or renal transplantation
- Severe liver function impairment (alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 3 times the upper limit of normal value）
- Severe pulmonary disease including pulmonary hypertension (clinical diagnosis)
- Uncontrollable hypertension or diabetes mellitus
- Contraindications to anticoagulants or antiplatelet drugs, either before or after the PFO closure procedure
- Active or planned (within 12 months) pregnancy, or lactating female patients
- Patients with hypercoagulable states
- Patients diagnosed with a neurological disease that causes progressive neurological dysfunction
- Malignant tumors or other serious diseases resulting in a life expectancy of less than 12 months
- Anatomy in which the device would interfere with intracardiac or vascular structures
- Psychiatric conditions that may interfere with medical compliance and compliance with follow-up
- Patient is currently participating in another investigational drug or device study that has not reached its primary endpoint yet
- Patient with any medical condition that would make him/her inappropriate for treatment as per the current IFU of respective devices or in the opinion of the Investigator
- Inability to obtain Informed Consent from patient or legally authorized representatives
- Stroke with poor outcome at time of enrollment (Modified Rankin score >3)
- Subjects who will not be available for follow up for the duration of the trial
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Único
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
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Experimental: Cocoon PFO Occluder - experimental
Participants undergo percutaneous closure of patent foramen ovale (PFO) using the Cocoon PFO Occluder device. The procedure is performed under standard clinical practice. Follow-up includes echocardiographic assessment of PFO closure and routine clinical evaluations. Participants are assigned to the two study arms using a 3:1 randomization scheme (Cocoon PFO Occluder : Amplatzer PFO Occluder). |
Percutaneous PFO closure performed according to standard clinical practice. The procedure is scheduled within 45 days after randomization and includes initiation of dual antiplatelet therapy before the intervention. Closure is performed following the Instructions for Use (IFU) of the assigned device and is guided by intracardiac echocardiography or transesophageal echocardiography. After device implantation, patients undergo routine post-procedure assessment and are instructed to follow antiplatelet therapy consistent with European clinical practice guidelines. Endocarditis prophylaxis is recommended for six months. The procedural steps are identical for both study arms; the only difference is the device implanted (Cocoon PFO Occluder or Amplatzer PFO Occluder). Participants are assigned to the two study arms using a 3:1 randomization scheme (Cocoon PFO Occluder : Amplatzer PFO Occluder). |
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Comparador activo: Amplatzer PFO Occluder - Control
Participants undergo percutaneous closure of patent foramen ovale (PFO) using the Amplatzer PFO Occluder device, considered the current standard of care. Follow-up includes echocardiographic assessment of PFO closure and routine clinical evaluations. Participants are assigned to the two study arms using a 3:1 randomization scheme (Cocoon PFO Occluder : Amplatzer PFO Occluder). |
Percutaneous PFO closure performed according to standard clinical practice. The procedure is scheduled within 45 days after randomization and includes initiation of dual antiplatelet therapy before the intervention. Closure is performed following the Instructions for Use (IFU) of the assigned device and is guided by intracardiac echocardiography or transesophageal echocardiography. After device implantation, patients undergo routine post-procedure assessment and are instructed to follow antiplatelet therapy consistent with European clinical practice guidelines. Endocarditis prophylaxis is recommended for six months. The procedural steps are identical for both study arms; the only difference is the device implanted (Cocoon PFO Occluder or Amplatzer PFO Occluder). Participants are assigned to the two study arms using a 3:1 randomization scheme (Cocoon PFO Occluder : Amplatzer PFO Occluder). |
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Composite endpoint of recurrent ischemic stroke, TIA, or all-cause death at 12 months
Periodo de tiempo: 12 months after the procedure
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A non-inferiority comparison between the Cocoon PFO Occluder and the Amplatzer PFO Occluder in terms of a composite endpoint including:
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12 months after the procedure
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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PFO Closure Rate
Periodo de tiempo: 6 months
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Complete closure is defined as right-to-left shunt (RLS) grade 0. Effective closure is defined as RLS grade 0 or 1 on imaging (TTE as default, TOE when clinically indicated) |
6 months
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Composite of Recurrent Ischemic Stroke, TIA, or Death
Periodo de tiempo: 30 days and 6 months
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Composite endpoint including recurrent ischemic stroke, TIA (neurologist-confirmed), or all-cause mortality. |
30 days and 6 months
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Neurological Death
Periodo de tiempo: 30 days, 6 months, 12 months
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Death attributable to neurological causes. |
30 days, 6 months, 12 months
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Cardiovascular Death
Periodo de tiempo: 30 days, 6 months, 12 months
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Death attributable to cardiovascular causes. |
30 days, 6 months, 12 months
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Recurrent Symptomatic Non-Fatal Stroke
Periodo de tiempo: 30 days, 6 months, 12 months
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TIA defined according to the same criteria as the primary endpoint and confirmed by a neurologist |
30 days, 6 months, 12 months
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Serious Adverse Events (SAE)
Periodo de tiempo: 30 days, 6 months, 12 months
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Incidence of any serious adverse event as defined by standard reporting criteria. |
30 days, 6 months, 12 months
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Device- or Procedure-Related Serious Adverse Events
Periodo de tiempo: 30 days, 6 months, 12 months
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SAE related to the device or procedure, including but not limited to: death, systemic embolism, device embolization or malposition, device thrombosis, cardiac injury/perforation, pericardial tamponade/effusion, endocarditis, atrial fibrillation, and severe vascular access complications |
30 days, 6 months, 12 months
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Clinically Significant New Atrial Arrhythmia
Periodo de tiempo: 30 days, 6 months, 12 months
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New atrial arrhythmia (including AF) confirmed by ECG, Holter, or approved monitoring device. AF defined per international guidelines (≥30-second episode with absence of P waves and irregular RR intervals). |
30 days, 6 months, 12 months
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Device Success
Periodo de tiempo: Immediately after the procedure
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Successful delivery, deployment at intended site, and retrieval of the delivery system. |
Immediately after the procedure
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Procedural Success
Periodo de tiempo: At hospital discharge
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Device success without device- or procedure-related SAE prior to discharge |
At hospital discharge
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Change in Monthly Migraine Days
Periodo de tiempo: Months 9-12 vs. baseline (3 months before implantation)
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Change in monthly migraine days in patients with a neurologist-confirmed diagnosis of migraine. |
Months 9-12 vs. baseline (3 months before implantation)
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Quality of Life (SF-36 Score)
Periodo de tiempo: 6 months, 12 months
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Assessment of quality of life using the SF-36 questionnaire. |
6 months, 12 months
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Systemic Embolism
Periodo de tiempo: 30 days, 6 months, 12 months
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Incidence of systemic embolic events confirmed clinically or by imaging |
30 days, 6 months, 12 months
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Possible/Probable Device-Related Allergy
Periodo de tiempo: 12 months
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Device-related allergic reactions adjudicated by the Clinical Events Committee (CEC) |
12 months
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Echocardiographic Markers of Device Endothelialization
Periodo de tiempo: At 6 months (±1 month) post-procedure At 12 months (±2 months) post-procedure Additional TOE as clinically indicated through study completion (up to 12 months)
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Evaluation of endothelialization using surrogate TOE markers: device surface echogenicity, peri-device flow, presence of thrombus/mass, visible disc surface area, and bubble contrast washout. Data will be summarized as the proportion of participants meeting criteria for complete endothelialization at each follow-up time point. |
At 6 months (±1 month) post-procedure At 12 months (±2 months) post-procedure Additional TOE as clinically indicated through study completion (up to 12 months)
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Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Investigador principal: Giuseppe Tarantini, MD, PhD, FESC, University of Padova
Publicaciones y enlaces útiles
Publicaciones Generales
- 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.
- Lee PH, Song JK, Kim JS, Heo R, Lee S, Kim DH, Song JM, Kang DH, Kwon SU, Kang DW, Lee D, Kwon HS, Yun SC, Sun BJ, Park JH, Lee JH, Jeong HS, Song HJ, Kim J, Park SJ. Cryptogenic Stroke and High-Risk Patent Foramen Ovale: The DEFENSE-PFO Trial. J Am Coll Cardiol. 2018 May 22;71(20):2335-2342. doi: 10.1016/j.jacc.2018.02.046. Epub 2018 Mar 12.
- Carroll JD, Saver JL, Thaler DE, Smalling RW, Berry S, MacDonald LA, Marks DS, Tirschwell DL; RESPECT Investigators. Closure of patent foramen ovale versus medical therapy after cryptogenic stroke. N Engl J Med. 2013 Mar 21;368(12):1092-100. doi: 10.1056/NEJMoa1301440.
- 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.
- Testa L, Popolo Rubbio A, Squillace M, Albano F, Cesario V, Casenghi M, Tarantini G, Pagnotta P, Ielasi A, Popusoi G, Paloscia L, Durante A, Maffeo D, Meucci F, Valentini G, Ussia GP, Cioffi P, Cortese B, Sangiorgi G, Contegiacomo G, Bedogni F. Patent foramen ovale occlusion with the Cocoon PFO Occluder. The PROS-IT collaborative project. Front Cardiovasc Med. 2023 Jan 11;9:1064026. doi: 10.3389/fcvm.2022.1064026. eCollection 2022.
- Meier B, Kalesan B, Mattle HP, Khattab AA, Hildick-Smith D, Dudek D, Andersen G, Ibrahim R, Schuler G, Walton AS, Wahl A, Windecker S, Juni P; PC Trial Investigators. Percutaneous closure of patent foramen ovale in cryptogenic embolism. N Engl J Med. 2013 Mar 21;368(12):1083-91. doi: 10.1056/NEJMoa1211716.
- Furlan AJ, Reisman M, Massaro J, Mauri L, Adams H, Albers GW, Felberg R, Herrmann H, Kar S, Landzberg M, Raizner A, Wechsler L; CLOSURE I Investigators. Closure or medical therapy for cryptogenic stroke with patent foramen ovale. N Engl J Med. 2012 Mar 15;366(11):991-9. doi: 10.1056/NEJMoa1009639.
- Pristipino C, Sievert H, D'Ascenzo F, Mas JL, Meier B, Scacciatella P, Hildick-Smith D, Gaita F, Toni D, Kyrle P, Thomson J, Derumeaux G, Onorato E, Sibbing D, Germonpre P, Berti S, Chessa M, Bedogni F, Dudek D, Hornung M, Zamorano J; European Association of Percutaneous Cardiovascular Interventions (EAPCI); European Stroke Organisation (ESO); European Heart Rhythm Association (EHRA); European Association for Cardiovascular Imaging (EACVI); Association for European Paediatric and Congenital Cardiology (AEPC); ESC Working group on GUCH; ESC Working group on Thrombosis; European Haematological Society (EHA). European position paper on the management of patients with patent foramen ovale. General approach and left circulation thromboembolism. EuroIntervention. 2019 Jan 20;14(13):1389-1402. doi: 10.4244/EIJ-D-18-00622. No abstract available.
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Trastornos cerebrovasculares
- Enfermedades Cerebrales
- Enfermedades del Sistema Nervioso Central
- Enfermedades del Sistema Nervioso
- Enfermedades Vasculares
- Enfermedades cardiovasculares
- Enfermedades cardíacas
- Isquemia cerebral
- Anomalías congénitas
- Anomalías cardiovasculares
- Defectos Cardíacos Congénitos
- Defectos del tabique cardíaco, auricular
- Defectos del tabique cardíaco
- Enfermedades y anomalías congénitas, hereditarias y neonatales
- Accidente cerebrovascular isquémico
- Carrera
- Ataque Isquémico, Transitorio
- Foramen oval permeable
Otros números de identificación del estudio
- SAFE-PFO
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
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