Comparing Two PFO Closure Devices in Adults With Previous Stroke or TIA

NCT07380490 | Not Yet Recruiting

• 1 other identifier: SAFE-PFO
• Study Type: interventional
• Target: 1,260
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Patent Foramen Ovale; Stroke; Transient Ischemic Attack (TIA)

Keywords

PFO Closure; Cocoon PFO Occluder; Amplatzer PFO Occluder; Patent Foramen Ovale; Cryptogenic Stroke; Transient Ischemic Attack

Outcome Measures

Primary Outcomes (1)

• Composite endpoint of recurrent ischemic stroke, TIA, or all-cause death at 12 months

  A non-inferiority comparison between the Cocoon PFO Occluder and the Amplatzer PFO Occluder in terms of a composite endpoint including: 1. Recurrent ischemic stroke, defined as an acute focal neurological deficit presumed to result from focal ischemia, with symptoms lasting ≥24 hours, or \<24 hours if accompanied by MRI or CT evidence of a new, anatomically relevant cerebral infarct. 2. Transient ischemic attack (TIA), defined as an acute focal neurological deficit (e.g., focal motor deficit, aphasia, gait disturbance, hemisensory deficit, amaurosis fugax, blindness, or focal visual deficit) presumed due to focal ischemia, lasting between 5 minutes and 24 hours, and not associated with MRI or CT evidence of a new infarct. Clinical evaluation by a neurologist is required. 3. All-cause mortality.

  12 months after the procedure

Secondary Outcomes (15)

• PFO Closure Rate

  6 months

• Composite of Recurrent Ischemic Stroke, TIA, or Death

  30 days and 6 months

• Neurological Death

  30 days, 6 months, 12 months

• Cardiovascular Death

  30 days, 6 months, 12 months

• Recurrent Symptomatic Non-Fatal Stroke

  30 days, 6 months, 12 months

Study Arms (2)

Cocoon PFO Occluder - experimental

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).

Device: PFO Closure procedure

Amplatzer PFO Occluder - Control

ACTIVE COMPARATOR

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).

Device: PFO Closure procedure

Interventions

PFO Closure procedure DEVICE

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).

Amplatzer PFO Occluder - Control; Cocoon PFO Occluder - experimental

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Giuseppe Tarantini: lead
• Sahajanand Medical Technologies Limited: collaborator

Related Publications (8)

• 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.

  PMID: 36712245 BACKGROUND

• 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.

  PMID: 29910193 BACKGROUND

• 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.

  PMID: 29544871 BACKGROUND

• 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.

  PMID: 28902593 BACKGROUND

• 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.

  PMID: 23514286 BACKGROUND

• 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.

  PMID: 23514285 BACKGROUND

• 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.

  PMID: 22417252 BACKGROUND

• 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.

  PMID: 30141306 BACKGROUND

MeSH Terms

Conditions

Foramen Ovale, Patent; Stroke; Ischemic Attack, Transient; Ischemic Stroke

Condition Hierarchy (Ancestors)

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

Study Officials

• Giuseppe Tarantini, MD, PhD, FESC

  University of Padova

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Daniela Ramaccini, PhD, PharmaD

CONTACT

+39 3534390426; d.ramaccini@endocorelab.org

Francesco Cardaioli, MD

CONTACT

+39 338 1986562; francesco.cardaioli@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: The study is single-blind. Participants are masked to the device used (Cocoon vs. Amplatzer). Treating physicians and study staff involved in the procedure are not blinded due to the nature of the intervention. Participants may request unblinding at any time
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 25, 2025
• First Posted: February 2, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): April 1, 2028
• Last Updated: March 24, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share