Cryptogenic StrokeALFA-ROMEONCT04881578
Atrial Fibrillation Before and After Patent Foramen Ovale Closure Study
An observational study of Cryptogenic Stroke and Foramen Ovale, Patent, run by Raban Jeger at 6 sites in Switzerland.
Trial summary
The aim of the ALFA ROMEO study is to better understand the association between cryptogenic stroke, PFO, PFO closure and AF. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cryptogenic Stroke, Foramen Ovale, Patent, Atrial Fibrillation
- What is being tested?
- continuous cardiac monitoring before and after transcatheter PFO closure
- How many people
- 200 participants
- Where
- 6 sitesSwitzerland
- Study dates
- 31 Mar 2021to 30 Nov 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: patients with a history of systemic embolization, i.e., cryptogenic stroke or acute peripheral arterial closures, and a concomitant PFO
Who may be able to join
- 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
- Cardiac monitoring is planned to be performed with the BIOMONITOR III(m) device
Show all 10Show fewer
- 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.
- Occlusion of PFO is planned to be performed with the AMPLATZERTM PFO OCCLUDER device.
- Patient is willing to sign patient consent form.
- Age ≥18 years.
Who cannot join
- 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
- Atrial septal defect or ventricular septal defect.
Show all 14Show fewer
- Coronary or valvular disease requiring surgical intervention.
- Documented history of AF or atrial flutter.
- Permanent indication for therapeutic oral anticoagulation at enrollment.
- Already included in another clinical trial that will affect the objectives of this study.
- Life expectancy <1 year.
- Pregnancy.
- Patient underwent or is scheduled for implantation of a pacemaker, implantable cardioverter defibrillator or cardiac resynchronization therapy device.
- Unable or unwilling to follow the required procedures of the Clinical Investigation Plan.
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
Switzerland6 sites
University Hospital Basel, Heart Center
Basel, 4053
University Hospital Bern Inselspital Cardiology
Bern
Cantonal Hospital St.Gallen Cardiology
Sankt Gallen, 9007
Bürgerspital Solothurn Cardiology
Solothurn, 4500
Stadtspital Triemli
Zurich, Canton of Zurich, 8063
University Hospital Zürich Cardiology
Zurich, 8006
About this study
The aim of the ALFA ROMEO study is to better understand the association between cryptogenic stroke, PFO, PFO closure and AF.
Read the 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
- Being tested
- continuous cardiac monitoring before and after transcatheter PFO closure
- Keywords
- occlusion of patent foramen ovale
- Medical subject headings
- Ischemic Stroke, Foramen Ovale, Patent, Atrial Fibrillation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
continuous cardiac monitoring before and after transcatheter PFO closureOther
Data will be assessed from patients with cryptogenic stroke and planned PFO occlusion who undergo the contemporary ICM protocols to search for silent AF
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 12 months
Secondary outcomes (8)
Incidence of first AF within 3 months of continuous rhythm monitoring before the intended percutaneous PFO closure procedure
to assess the incidence of first AF within 3 months of continuous rhythm monitoring before PFo closure
Measured: 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
To assess the overall incidence of first AF from ICM-implantation to ICM-explantation or 36 months post implantation
Measured: 36 months
Differences in the primary endpoint according to the grade of the PFO
To assess the differences in the primary endpoint according to the grade of the PFO
Measured: 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)
To assess the incidence of recurrent clinical embolic events
Measured: 36 months
AF burden, defined as proportion of follow-up time with documented AF at different time points
To assess the AF burden
Measured: 36 months
Incidence of major bleeding (BARC 3 to 5)
To assess the incidence of major bleeding
Measured: 36 months
Incidence of any death and cardiovascular death at different timepoints
To assess the incicence of any death and cardiovascular death at diefferent timepoints
Measured: 36 months
Device related events
To assess device related events
Measured: 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 May 2021
- Study start31 Mar 2021
- Primary completion30 Nov 2027 (estimated)
- Study completion30 Nov 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cryptogenic StrokeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 200 participants (actual)
Sponsor and investigators
- Lead sponsor
- Raban Jeger
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Raban Jeger, University Hospital, Basel, Switzerland
- Investigators
- Raban Jeger, Prof Dr med, Principal investigator, University Hospital, Basel, SwitzerlandTobias Reichlin, Prof Dr med, Principal investigator, University Hospital Bern Inselspital, Switzerland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04881578
- Sponsor's protocol ID
- 2021-00016
- Acronym
- ALFA-ROMEO
- Status last verified
- May 2025
- First submitted
- 5 May 2021
- Last updated
- 13 May 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Atrial Fibrillation Before and After Patent Foramen Ovale Closure Study
- ClinicalTrials.gov ID
- NCT04881578
- Acronym / sponsor ID
- ALFA-ROMEO / 2021-00016
- Keywords
- occlusion of patent foramen ovale
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 200 participants (actual)
- Lead sponsor
- Raban JegerUniversity, hospital or other
- Study start
- 31 Mar 2021 (actual)
- Primary completion
- 30 Nov 2027 (estimated)
- Study completion
- 30 Nov 2027 (estimated)
- First posted
- 11 May 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of the ALFA ROMEO study is to better understand the association between cryptogenic stroke, PFO, PFO closure and AF.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- patients with a history of systemic embolization, i.e., cryptogenic stroke or acute peripheral arterial closures, and a concomitant PFO
Key inclusion criteria (10 listed)
- 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:
- Cardiac monitoring is planned to be performed with the BIOMONITOR III(m) device
- 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.
- Occlusion of PFO is planned to be performed with the AMPLATZERTM PFO OCCLUDER device.
- Patient is willing to sign patient consent form.
Key exclusion criteria (14 listed)
- Known etiology of the embolic event (based on neuro-/cardiac/vascular imaging), such as:
- Atrial septal defect or ventricular septal defect.
- Coronary or valvular disease requiring surgical intervention.
- Documented history of AF or atrial flutter.
- Permanent indication for therapeutic oral anticoagulation at enrollment.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| continuous cardiac monitoring before and after transcatheter PFO closureData will be assessed from patients with cryptogenic stroke and planned PFO occlusion who undergo the contemporary ICM protocols to search for silent AF | Other | – |
Primary outcome
incidence of first AF within 12 months after percutaneous PFO occlusion
Time frame: 12 months
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)
8 secondary outcomes
Incidence of first AF within 3 months of continuous rhythm monitoring before the intended percutaneous PFO closure procedure
Time frame: 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
Time frame: 36 months
Differences in the primary endpoint according to the grade of the PFO
Time frame: 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)
Time frame: 36 months
AF burden, defined as proportion of follow-up time with documented AF at different time points
Time frame: 36 months
Incidence of major bleeding (BARC 3 to 5)
Time frame: 36 months
Incidence of any death and cardiovascular death at different timepoints
Time frame: 36 months
Device related events
Time frame: 36 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 May 2025.
- Individual participant dataSharing planned: No
Related trials for Cryptogenic Stroke
Recruiting
Discontinuation of Antithrombotic Treatment Following Patent Foramen Ovale Closure in Young Patients With Cryptogenic Stroke
Patent Foramen Ovale, Ischemic Stroke
Not yet recruiting
CATCH AF - Atrial Fibrillation Detection in Cryptogenic Stroke
Atrial Fibrillation (AF)
RecruitingObservational study
Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
Rare Disorders, Undiagnosed Disorders
RecruitingPhase 4
NeuroAiD Patient-Reported Outcomes in Patients With Mild to Moderate Ischemic Stroke
Stroke, Stroke, Acute Ischemic
Recruiting
Intensive Cancer Screening After Cryptogenic Stroke
Occult Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Raban Jeger, Prof Dr med principal investigator
University Hospital, Basel, Switzerland
Tobias Reichlin, Prof Dr med principal investigator
University Hospital Bern Inselspital, Switzerland
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cryptogenic Stroke and Foramen Ovale, Patent, run by Raban Jeger at 6 sites in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 13 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
incidence of first AF within 12 months after percutaneous PFO occlusion (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 May 2025.