PFO tRanscatether Occlusion Long-term Outcomes National Group (PROLONG) Registry (PROLONG)

Patent foramen ovale (PFO) has been associated with cryptogenic stroke and transient ischemic attack (TIA) in young adults.

Evidence from randomized clinical trials (RCT) has shown that transcatheter PFO closure yields a 59% relative reduction in recurrent ischemic stroke compared to medical therapy in selected individuals.

However, the follow-up duration in these studies averaged around 4 years, while only two studies report a median follow-up beyond 10 years. Considering the relative youth of the patients undergoing this procedure (average age being under 50 years across all studies), we can reasonably anticipate a substantial post-PFO closure lifespan for these individuals. Consequently, it is imperative to gather more extensive long-term follow-up data among PFO closure recipients The PROLONG (PFO tRanscatether Occlusion Long-term Outcomes National Group) is an observational, retrospective, multicenter, national registry including men and women undergoing transcatheter PFO closure, with the aim of assessing the long-term (>10 years) efficacy and safety of this procedure.

Study Overview

• Status: Completed
• Conditions: Patent Foramen Ovale; Atrial Fibrillation New Onset; Stroke, Cryptogenic; Transient Ischaemic Attack Due to Embolism
• Intervention / Treatment: Device: Septal Occluder Device

Detailed Description

The PROLONG (PFO Transcatheter Occlusion Long-term Outcomes National Group) is an observational, retrospective, multicenter registry. It includes 1,360 subjects who underwent transcatheter patent foramen ovale (PFO) closure between 1999 and 2013 at 12 Italian high-volume Centers. Patients will have at least 10 years of follow-up post-procedure.

The primary objectives of the study are to evaluate the long-term clinical effectiveness of PFO closure by the incidence of left-sided embolic events and to evaluate safety by assessing serious device- or procedure-related adverse events. Secondary objectives include the incidence of new-onset atrial arrhythmias, the presence and severity of residual shunts, the incidence and severity of migraine symptoms, and bleeding events.

• Study Type: Observational
• Enrollment (Actual): 1360

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The PROLONG registry will enroll a total of 1360 subjects who underwent transcatheter patent foramen ovale (PFO) closure between 1999 and 2013 at 12 high-volume Italian Centers.

Subjects range in age and gender and encompass individuals from both urban and rural areas, representing a comprehensive sample of patients typically seen in a real-world clinical setting.

Description

Inclusion Criteria:

• Age ≥18 years;
• Confirmed Patent Foramen Ovale (PFO);
• Transcatheter Patent Foramen Ovale (PFO) closure with an Occluder device;
• PFO closure procedure performed between 1999 and 2013.

Exclusion Criteria:

• Age < 18 years;
• Previous surgical or transcatheter PFO closure;
• Patients without follow-up data available.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Device Closure; PFO closure with septal occluder device.	Device: Septal Occluder Device; Transcatheter PFO closure with any commercially available septal occluder device

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with ischemic stroke, transient ischemic attack or systemic embolism (SE) post device implant (Primary Effectiveness Outcome)	The primary effectiveness outcome is the composite incidence of stroke, transient ischemic attack (TIA), and systemic embolism (SE) post-PFO closure.	Duration of follow-up (minimum of 10 years)
Number of Participants with device- or procedure-related serious adverse events (Primary Safety Endpoint)	Device- or procedure- related serious adverse events post device implant	Duration of follow-up (minimum of 10 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with recurrent ischemic stroke	Incidence of ischemic stroke post-PFO closure.	Time Frame: Duration of follow-up (minimum of 10 years)
Number of Participants withrecurrent transient ischemic attack (TIA)	Incidence of transient ischemic attack (TIA) post-PFO closure.	Time Frame: Duration of follow-up (minimum of 10 years)
Number of Participants with with recurrent systemic embolism (SE)	Incidence of systemic embolism (SE) post-PFO closure.	Time Frame: Duration of follow-up (minimum of 10 years)
Rate of Procedural Success	The rate of successful PFO closure as determined by the absence of severe residual shunt or any procedure- or device-related serious adverse event (SAE)	Time Frame: Duration of follow-up (minimum of 10 years)
Incidence of Clinically Significant New Atrial Arrhythmia	The occurrence of new-onset atrial fibrillation (AF) or atrial flutter (AFL) following PFO-closure	Time Frame: Duration of follow-up (minimum of 10 years)
Rate of All-cause mortality	The overall mortality rate of patients post-PFO closure, including both cardiac and non-cardiac causes, documented during follow-up.	Time Frame: Duration of follow-up (minimum of 10 years)
Rate of residual shunt	Characterization of presence and severity of a residual shunt post-PFO closure, as detected by follow-up echocardiographic assessments.	Time Frame: Duration of follow-up (minimum of 10 years)
Incidence of Device-Related and procedure-related Complications	The rate of complications related to the PFO closure device, such as device embolization, erosion, or thrombosis, documented during follow-up.	Time Frame: Duration of follow-up (minimum of 10 years)
Incidence of bleeding events	The rate of bleeding events according to the Bleeding Academic Research Consortium (BARC) criteria	Time Frame: Duration of follow-up (minimum of 10 years)
Incidence of migraine symptoms	The presence and severity of migraine symptoms will be documented	Time Frame: Duration of follow-up (minimum of 10 years)

Collaborators and Investigators

• Sponsor: IRCCS Ospedale San Raffaele
• Collaborators: Fondazione Policlinico Universitario Agostino Gemelli IRCCS; IRCCS Azienda Ospedaliero-Universitaria di Bologna; University Of Perugia; Maria Cecilia Hospital; Azienda Ospedaliero Universitaria Maggiore della Carita; University Hospital Padova; Centro Cardiologico Monzino; Azienda Policlinico Umberto I; San Camillo Hospital, Rome; Clinica San Martino

Publications and helpful links

General Publications

• 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.
• Saver JL, Carroll JD, Thaler DE, Smalling RW, MacDonald LA, Marks DS, Tirschwell DL; RESPECT Investigators. Long-Term Outcomes of Patent Foramen Ovale Closure or Medical Therapy after Stroke. N Engl J Med. 2017 Sep 14;377(11):1022-1032. doi: 10.1056/NEJMoa1610057.
• 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.
• Mendelson SJ, Prabhakaran S. Diagnosis and Management of Transient Ischemic Attack and Acute Ischemic Stroke: A Review. JAMA. 2021 Mar 16;325(11):1088-1098. doi: 10.1001/jama.2020.26867.
• Wintzer-Wehekind J, Alperi A, Houde C, Cote JM, Asmarats L, Cote M, Rodes-Cabau J. Long-Term Follow-Up After Closure of Patent Foramen Ovale in Patients With Cryptogenic Embolism. J Am Coll Cardiol. 2019 Jan 29;73(3):278-287. doi: 10.1016/j.jacc.2018.10.061.
• Pristipino C, Sievert H, D'Ascenzo F, Louis Mas J, 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; Evidence Synthesis Team; Eapci Scientific Documents and Initiatives Committee; International Experts. European position paper on the management of patients with patent foramen ovale. General approach and left circulation thromboembolism. Eur Heart J. 2019 Oct 7;40(38):3182-3195. doi: 10.1093/eurheartj/ehy649. Erratum In: Eur Heart J. 2021 May 7;42(18):1807. doi: 10.1093/eurheartj/ehab176.
• Kuijpers T, Spencer FA, Siemieniuk RAC, Vandvik PO, Otto CM, Lytvyn L, Mir H, Jin AY, Manja V, Karthikeyan G, Hoendermis E, Martin J, Carballo S, O'Donnell M, Vartdal T, Baxter C, Patrick-Lake B, Scott J, Agoritsas T, Guyatt G. Patent foramen ovale closure, antiplatelet therapy or anticoagulation therapy alone for management of cryptogenic stroke? A clinical practice guideline. BMJ. 2018 Jul 25;362:k2515. doi: 10.1136/bmj.k2515. No abstract available.
• Vaduganathan M, Qamar A, Gupta A, Bajaj N, Golwala HB, Pandey A, Bhatt DL. Patent Foramen Ovale Closure for Secondary Prevention of Cryptogenic Stroke: Updated Meta-Analysis of Randomized Clinical Trials. Am J Med. 2018 May;131(5):575-577. doi: 10.1016/j.amjmed.2017.11.027. Epub 2017 Dec 8.
• Ahmad Y, Howard JP, Arnold A, Shin MS, Cook C, Petraco R, Demir O, Williams L, Iglesias JF, Sutaria N, Malik I, Davies J, Mayet J, Francis D, Sen S. Patent foramen ovale closure vs. medical therapy for cryptogenic stroke: a meta-analysis of randomized controlled trials. Eur Heart J. 2018 May 7;39(18):1638-1649. doi: 10.1093/eurheartj/ehy121.
• Mojadidi MK, Elgendy AY, Elgendy IY, Mahmoud AN, Elbadawi A, Eshtehardi P, Patel NK, Wayangankar S, Tobis JM, Meier B. Transcatheter Patent Foramen Ovale Closure After Cryptogenic Stroke: An Updated Meta-Analysis of Randomized Trials. JACC Cardiovasc Interv. 2017 Nov 13;10(21):2228-2230. doi: 10.1016/j.jcin.2017.09.002. No abstract available. Erratum In: JACC Cardiovasc Interv. 2018 May 14;11(9):918-919. doi: 10.1016/j.jcin.2018.04.021.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 1999
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): June 1, 2024

Study Registration Dates

• First Submitted: July 4, 2024
• First Submitted That Met QC Criteria: July 10, 2024
• First Posted (Actual): July 16, 2024

Study Record Updates

• Last Update Posted (Actual): July 16, 2024
• Last Update Submitted That Met QC Criteria: July 10, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Stroke; Atrial Fibrillation; Patent Foramen Ovale; Transient Ischemic Attack; Stroke, Cryptogenic; Interventional cardiology
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Congenital Abnormalities; Embolism and Thrombosis; Arrhythmias, Cardiac; Brain Ischemia; Stroke; Heart Defects, Congenital; Cardiovascular Abnormalities; Heart Septal Defects, Atrial; Heart Septal Defects; Ischemic Stroke; Embolism; Ischemic Attack, Transient; Atrial Fibrillation; Foramen Ovale, Patent
• Other Study ID Numbers: 09031943

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No