Atrial Fibrillation Before and After Patent Foramen Ovale Closure Study (ALFA ROMEO)

The aim of the ALFA ROMEO study is to better understand the association between cryptogenic stroke, PFO, PFO closure and AF.

Study Overview

• Status: Recruiting
• Conditions: Atrial Fibrillation; Foramen Ovale, Patent; Cryptogenic Stroke
• Intervention / Treatment: Other: continuous cardiac monitoring before and after transcatheter PFO closure

Detailed Description

For patients with cryptogenic stroke and PFO, a better understanding of the exact incidence of new-onset AF before and after PFO closure, its occurrence during follow-up, its persistence or reversibility and its prognostic impact is critical: If only a PFO, but no AF is available, then PFO closure followed by a limited duration of antiplatelet therapy is indicated. If on the other hand side a PFO and AF is found, lifelong therapeutic anticoagulation is mandatory.

By using the contemporary ICM protocols to search for silent AF in patients with cryptogenic stroke and a PFO for 3 months before PFO closure, ALFA ROMEO will help to understand the relationship of silent and previously undetected AF in the setting of PFO and investigate the true incidence of new-onset AF and its temporal course after effective PFO closure. Our findings will have the potential to impact on the future diagnostic and therapeutic management of patients with cryptogenic stroke and a PFO

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

• Study Contact: Name: Raban Jeger, Prof Dr med; Phone Number: +41 61 265 25 25; Email: raban.jeger@usb.ch
• Study Contact Backup: Name: Nicole Gilgen, Dr med; Phone Number: +41 61 265 25 25; Email: nicole.gilgen@usb.ch

Study Locations

• Switzerland
  • Aarau, Switzerland, 5001
    • Withdrawn
    • Cantonal Hospital Aarau Cardiology
  • Basel, Switzerland, 4053
    • Recruiting
    • University Hospital Basel, Heart Center
    • Contact: Raban Jeger, Prof Dr med; Phone Number: +41 61 265 25 25; Email: raban.jeger@usb.ch
    • Contact: Nicole Gilgen, Dr med; Phone Number: +41 61 265 25 25; Email: nicole.gilgen@usb.ch
    • Principal Investigator: Christoph Ado Kaiser, Prof Dr med
  • Bern, Switzerland
    • Recruiting
    • University Hospital Bern Inselspital Cardiology
    • Contact: Tobias Reichlin, Prof Dr med; Phone Number: +41 31 632 21 11; Email: tobias.reichlin@insel.ch
  • Solothurn, Switzerland, 4500
    • Recruiting
    • Bürgerspital Solothurn Cardiology
    • Contact: Rolf Vogel, Prof Dr med et phil nat; Phone Number: +41 32 627 31 21; Email: Rolf.Vogel@spital.so.ch
    • Sub-Investigator: Tilmann Perrin, Dr med
  • St.gallen, Switzerland, 9007
    • Recruiting
    • Cantonal Hospital St.Gallen Cardiology
    • Contact: Daniel Weilenmann, Dr med; Phone Number: +41 71 494 11 11; Email: Daniel.Weilenmann@kssg.ch
  • Zürich, Switzerland, 8006
    • Recruiting
    • University Hospital Zürich Cardiology
    • Contact: Alexander Breitenstein, PD Dr med; Phone Number: 141 44 255 11 11; Email: Alexander.Breitenstein@usz.ch
  • Zürich, Switzerland, 8063
    • Recruiting
    • Stadtspital Triemli
    • Contact: David Kurz, PD Dr; Phone Number: +41 44 416 11 11; Email: david.kurz@stadtspital.ch
    • Principal Investigator: David Kurz, PD Dr
    • Principal Investigator: Raban Jeger, Prof Dr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

patients with a history of systemic embolization, i.e., cryptogenic stroke or acute peripheral arterial closures, and a concomitant PFO

Description

Inclusion Criteria:

1. History of embolic events such as cryptogenic stroke or systemic embolism (single event or multiple events). A stroke is considered to be cryptogenic if no possible cause can be determined despite extensive workup according to the standard protocol of the participating center (TOAST classification 5b) (29). Before inclusion in the study, the following tests are required as standard tests to establish the diagnosis of cryptogenic stroke:

   • MRI or computed tomography (CT) of the neurocranium (documenting ischemic embolic stroke)
   • 12-lead ECG (exclusion of AF)
   • Continuous ECG monitoring for at least 7 days (inpatient telemetry or Holter-ECG as an in- or outpatient
   • Ultrasonography, CT or MRI angiography of head and neck to rule out arterial disease as a cause of stroke (see below), or other potential causes of stroke
2. Cardiac monitoring is planned to be performed with the BIOMONITOR III(m) device
3. Presence of right-to-left shunt through a PFO as assessed by means of transesophageal echocardiography (TEE) with agitated saline while the patient is at rest or while a Valsalva maneuver is being performed.
4. Occlusion of PFO is planned to be performed with the AMPLATZERTM PFO OCCLUDER device.
5. Patient is willing to sign patient consent form.
6. Age ≥18 years.

Exclusion Criteria:

1. Known etiology of the embolic event (based on neuro-/cardiac/vascular imaging), such as:

   • Evidence of large-artery atherosclerosis (ultrasonography, CT or MRI angiography, or digital subtraction angiography) with stenosis of 50% or more in the artery feeding the acute ischemic territory.
   • Small vessel disease, defined by radiographic appearance consistent with ischemic infarction in the territory of a perforating arteriole, with ≤20 mm in diameter on axial sections and not involving the cortex, located in the white matter, internal or external capsule, deep brain nuclei, thalamus, or brainstem.
   • Evidence of a high-risk cardiac or aortic arch source of embolism (left ventricular or left atrial thrombus or "smoke," emboligenic valvular lesion or tumor, aortic arch plaque >3 mm thick or with mobile components or any other high-risk lesion)
   • Stroke of other determined cause such as presence of non-atherosclerotic vasculopathies (i.e. dissection, fibromuscular dysplasia), hypercoagulable states (must be tested in patients <55 years old) and hematologic disorders
2. Atrial septal defect or ventricular septal defect.
3. Coronary or valvular disease requiring surgical intervention.
4. Documented history of AF or atrial flutter.
5. Permanent indication for therapeutic oral anticoagulation at enrollment.
6. Already included in another clinical trial that will affect the objectives of this study.
7. Life expectancy <1 year.
8. Pregnancy.
9. Patient underwent or is scheduled for implantation of a pacemaker, implantable cardioverter defibrillator or cardiac resynchronization therapy device.
10. Unable or unwilling to follow the required procedures of the Clinical Investigation Plan.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
incidence of first AF within 12 months after percutaneous PFO occlusion	to assess the incidence of first AF within 12 months after percutaneous PFO closure with a prespecified landmark analysis after 3 months to differentiate potentially device related AF (months 0-3) from likely intrinsic AF (months 4-12)	12 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Incidence of first AF within 3 months of continuous rhythm monitoring before the intended percutaneous PFO closure procedure	3 months
Overall incidence of first AF from ICM-implantation to ICM-explantation or 36 months post implantation (if ICM remains in situ) excluding a blanking period of the first 3 months after PFO closure	36 months
Differences in the primary endpoint according to the grade of the PFO	12 months
Incidence of recurrent clinical embolic events such as cryptogenic strokes or systemic embolism including pulmonary embolism (with the use of the TOAST classification algorithm)	36 months
AF burden, defined as proportion of follow-up time with documented AF at different time points	36 months
Incidence of major bleeding (BARC 3 to 5)	36 months
Incidence of any death and cardiovascular death at different timepoints	36 months
Device related events	36 months

Collaborators and Investigators

• Sponsor: Raban Jeger
• Investigators: Principal Investigator: Raban Jeger, Prof Dr med, University Hospital, Basel, Switzerland; Principal Investigator: Tobias Reichlin, Prof Dr med, University Hospital Bern Inselspital, Switzerland

Study record dates

Study Major Dates

• Study Start (Actual): March 31, 2021
• Primary Completion (Estimated): May 31, 2027
• Study Completion (Estimated): May 31, 2027

Study Registration Dates

• First Submitted: May 5, 2021
• First Submitted That Met QC Criteria: May 5, 2021
• First Posted (Actual): May 11, 2021

Study Record Updates

• Last Update Posted (Actual): March 13, 2024
• Last Update Submitted That Met QC Criteria: March 12, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: occlusion of patent foramen ovale
• 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; Arrhythmias, Cardiac; Stroke; Heart Defects, Congenital; Cardiovascular Abnormalities; Heart Septal Defects, Atrial; Heart Septal Defects; Ischemic Stroke; Atrial Fibrillation; Foramen Ovale, Patent
• Other Study ID Numbers: 2021-00016

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No