Medical Treatment With or Without Transcatheter Patent Foramen Ovale Closure

Official title

Medical Treatment With or Without Transcatheter Patent Foramen Ovale CloSure for Older Patients With CrypTogenic StrOke and Patent Foramen Ovale. The STOP Trial

Overview

Patent foramen ovale PFO closure has been shown to reduce the risk of stroke in patients with recurrent stroke. However, the majority of existing clinical studies in this field excluded patients over the age of 60 years. Data in older patients is limited and since the population ages and stroke remains a major cause of death and morbidity, randomized clinical trials are needed to better assess the benefit of PFO closure in this elderly population. Therefore, this study proposal sought to determine the efficacy of PFO closure for the prevention of recurrent stroke in older patients with PFO and cryptogenic stroke.

Detailed description

Background and importance Consistent with studies performed in younger patient cohorts, older patients suffering a cryptogenic stroke exhibit a much higher prevalence of patent foramen ovale (PFO) compared to their stroke of known origin counterparts. Several studies have provided promising preliminary data regarding PFO closure in older patients with cryptogenic stroke, with very low stroke recurrence rates at mid- to long-term follow-up. Several randomized trials have shown the beneficial effects of PFO closure vs. medical treatment in patients younger than 60 years with cryptogenic stroke and PFO. Current observational data suggest similar or even more marked effects on stroke recurrence prevention of PFO closure in older patients and would support the design of a randomized trial to provide definite evidence in this field. Therefore, the objective of the present study is to evaluate the efficacy of transcatheter PFO closure for preventing recurrent ischemic stroke (nonlacunar) events in patients \>60 years diagnosed with a cryptogenic stroke and PFO.

Interventions

• Procedure Transcatheter PFO closure
  Transcatheter PFO closure procedure will be performed according to the standards and experience of each participating center. Any approved PFO occluder device will be allowed in the study. Patients will also receive antithrombotic agents (single antiplatelet treatment ), and modifiable vascular risk factors (dyslipidemia, hypertension, diabetes) according to stroke prevention guidelines. The type of antithrombotic therapy will be left to the discretion of the physician responsible for the patie
• Drug Optimal medical treatment
  Patients will receive antithrombotic agents (single antiplatelet treatment ), and modifiable vascular risk factors (dyslipidemia, hypertension, diabetes) according to stroke prevention guidelines. The type of antithrombotic therapy will be left to the discretion of the physician responsible for the patient.

Primary outcome measures

• Rate of ischemic events [Time frame: 12 months]

Secondary outcome measures (8)

• Rate of stroke events [Time frame: 12 months]
• Rate of mortality [Time frame: 10 year follow-up]
• Rate of cardiovascular mortality [Time frame: 10 year follow-up]
• Incidence of cerebral hemorrhage [Time frame: 10 year follow-up]
• Rate of new-onset atrial fibrillation [Time frame: 10 year follow-up]
• Rate of bleeding [Time frame: 10 year follow-up]
• Health-related quality of life [Time frame: 10 year follow-up]
• Neurocognitive assessment [Time frame: 10 year follow-up]

Eligibility criteria

Inclusion criteria

• Cryptogenic stroke
• Age >60 years
• Right-to-left shunt as evaluated by echocardiography (TEE).

Exclusion criteria

-≤60 year-old

• Lacunar (small vessel) stroke.
• Permanent or paroxysmal atrial fibrillation/flutter (clinically apparent or detected by continuous ECG monitoring).
• Need for chronic anticoagulation therapy.
• Any contraindication for antiplatelet therapy (aspirin, clopidogrel, ticagrelor).
• Presence of extracranial or intracranial atherosclerosis causing ≥50% luminal --stenosis in arteries supplying the area of ischemia.
• Presence of complex atheroma plaques at the ascending aorta-aortic arch (≥4-mm-thick, ulcerated or containing mobile thrombi) as evaluated by TEE.
• Presence of intracardiac thrombus as evaluated by TEE.
• Uncontrolled hypertension (systemic pressure values >160/90 mmHg despite optimal medical treatment).
• History of myocardial infarction or coronary intervention. (percutaneous coronary intervention, coronary artery bypass graft).
• History of prior valve surgery or transcatheter valve repair.
• Presence of deep venous thrombosis at the time of index stroke as evaluated by Doppler ultrasonography.
• Left ventricular ejection fraction <50% as evaluated by TTE.
• Significant (moderate or severe) valvular disease as evaluated by echocardiography.
• History of congestive heart failure.
• Severe chronic kidney dysfunction defined an estimated glomerular filtration rate <30 ml/min/m2 or need for dialysis.
• Isolated ASD or ASD associated with PFO but with a hemodynamically significant left-to-right shunt requiring closure.
• Other specific cause of stroke identified (eg, arteritis, dissection, migraine/vasospasm, and drug abuse).
• Prior surgical or endovascular treatments of PFO or ASD.
• Rheumatic heart disease.
• Left atrial enlargement defined as a left atrial diameter >41 mm in men and ≥39 mm in women.
• Presence of high burden of premature atrial contractions (>500 per 24 hrs) as evaluated by continuous ECG monitoring.
• Follow-up impossible or expected poor compliance.
• Active cancer.
• Presence of an inferior vena cava filter.
• Severe pulmonary artery hypertension (systolic pulmonary pressure >60 mmHg).
• Functional dependency as measured by a modified Rankin Scale score >3 (unable to attend to own bodily needs without assistance and unable to walk unassisted).
• Any medical condition determining a life expectancy <2 years.
• Participation in another randomized study.
• Failure to provide signed informed consent.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Canada · 2 centers

• IUCPQ-UL — Québec
• IUCPQ — Québec

Publications

• Kleindorfer DO, Towfighi A, Chaturvedi S, Cockroft KM, Gutierrez J, Lombardi-Hill D, Kamel H, Kernan WN, Kittner SJ, Leira EC, Lennon O, Meschia JF, Nguyen TN, Pollak PM, Santangeli P, Sharrief AZ, Smith SC Jr, Turan TN, Williams LS. 2021 Guideline for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack: A Guideline From the American Heart Association/American Stroke Ass PMID 34024117
• GBD 2016 Neurology Collaborators. Global, regional, and national burden of neurological disorders, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2019 May;18(5):459-480. doi: 10.1016/S1474-4422(18)30499-X. Epub 2019 Mar 14. PMID 30879893
• Tsao CW, Aday AW, Almarzooq ZI, Alonso A, Beaton AZ, Bittencourt MS, Boehme AK, Buxton AE, Carson AP, Commodore-Mensah Y, Elkind MSV, Evenson KR, Eze-Nliam C, Ferguson JF, Generoso G, Ho JE, Kalani R, Khan SS, Kissela BM, Knutson KL, Levine DA, Lewis TT, Liu J, Loop MS, Ma J, Mussolino ME, Navaneethan SD, Perak AM, Poudel R, Rezk-Hanna M, Roth GA, Schroeder EB, Shah SH, Thacker EL, VanWagner LB, V PMID 35078371
• Zhao W, Wu J, Liu J, Wu Y, Ni J, Gu H, Tu J, Wang J, An Z, Ning X. Trends in the incidence of recurrent stroke at 5 years after the first-ever stroke in rural China: a population-based stroke surveillance from 1992 to 2017. Aging (Albany NY). 2019 Mar 19;11(6):1686-1694. doi: 10.18632/aging.101862. PMID 30888967
• Cho KK, Khanna S, Lo P, Cheng D, Roy D. Persistent pathology of the patent foramen ovale: a review of the literature. Med J Aust. 2021 Jul;215(2):89-93. doi: 10.5694/mja2.51141. Epub 2021 Jul 4. PMID 34218432
• Molnar AA, Abraham P, Merkely B, Nardai S. Echocardiographic Evaluation of Atrial Communications before Transcatheter Closure. J Vis Exp. 2022 Feb 8;(180). doi: 10.3791/61240. PMID 35225286
• Ho SY, McCarthy KP, Rigby ML. Morphological features pertinent to interventional closure of patent oval foramen. J Interv Cardiol. 2003 Feb;16(1):33-8. doi: 10.1046/j.1540-8183.2003.08000.x. PMID 12664815
• Agarwal S, Bajaj NS, Kumbhani DJ, Tuzcu EM, Kapadia SR. Meta-analysis of transcatheter closure versus medical therapy for patent foramen ovale in prevention of recurrent neurological events after presumed paradoxical embolism. JACC Cardiovasc Interv. 2012 Jul;5(7):777-89. doi: 10.1016/j.jcin.2012.02.021. PMID 22814784

Identifiers

NCT: NCT05907694 · STOP

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗