An observational study in Ischemic Stroke, Atrial Fibrillation and Cerebrovascular Disorders, sponsored by Insel Gruppe AG, University Hospital Bern. Recruiting at 1 site in Switzerland. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-11-20.
Sponsored by Insel Gruppe AG, University Hospital Bern · Observational
Background
Atrial fibrillation (AF) is the most common cardiac arrhythmia, affecting up to 10% of the elderly. Ischemic stroke is the main complication of AF and cardioembolism is one of the leading causes of ischemic stroke, accounting for approximately one third of cases. Oral anticoagulant therapy (OAC) is a cornerstone in stroke prevention in patients with AF. According to randomized controlled trials of direct oral anticoagulants, a residual risk of ischemic stroke of 1-2% per year for so-called "breakthrough stroke" remains, despite adequate intake of OAC. The majority (>70%) of these breakthrough strokes are cardioembolic in nature and only a minority are related to medication issues (e.g. non-compliance) or other, non-AF related etiologies. Stroke recurrence risk after such a breakthrough stroke markedly increases to 8-9% per year indicating a particularly high-risk situation. Why OAC fails in certain patients, but not in others remains as poorly understood, as does the reason why the subsequent risk of stroke is so high.
Current risk stratification tools, such as the widely used CHA2DS2-VA(Sc)-score, fail to predict stroke risk in such a high-risk cohort, as they were intended to guide the initiation of OAC in low to moderate risk patients. In light of new therapeutic strategies currently being investigated, such as percutaneous left atrial appendage occlusion in patients with breakthrough strokes (ELAPSE - NCT05976685) or in AF-patients deemed high-risk (LAAOS IV - NCT05963698), improved risk stratification and characterization of high-risk AF patients is highly warranted.
Several clinical factors, such as those reflected in the CHA2DS2-VA(Sc)-score, and especially a high AF-burden are associated with increased risk of cardioembolic stroke. Several cardiac serum biomarkers are thought to be surrogates not only of cardiac function, but also of cardioembolic risk. Reflecting ventricular and atrial wall tension, myocardial injury, oxidative stress and thrombogenicity, elevated NT-proBNP, MR-proANP, high-sensitive Troponin T and D-Dimers have all been associated with cardioembolic stroke in different AF and non-AF populations. As the main location of thrombus formation, the left atrium (LA) and more specifically its appendage (LAA) are of particular interest in the pathogenesis of cardioembolism. Pronounced LA-enlargement, compared to a normal-sized LA, correlates with an increased risk of cardioembolism in AF-patients. As over 80% of thrombi form within the LAA, several LAA-characteristics, such as slower LAA-flow velocity and larger LAA-orifice area have also been demonstrated to be associated with higher stroke risk. Although there is data on each one of these factors, they have only been investigated in low to moderate risk populations, such as AF-patients without prior stroke, OAC-naïve patients, or even within the general population as a whole. Their role in high-risk AF-patients and in breakthrough stroke is unknown.
Hypothesis
The investigators hypothesize that specific clinical factors, serum cardiac biomarkers and markers of LA- and LAA-morphology and function are associated with breakthrough stroke / OAC-failure and may improve risk stratification.
Methods
CARE-AF is a single-center, prospective cohort study conducted at the Stroke Center of the Inselspital, University Hospital Bern, Switzerland. Patients with an index ischemic stroke and AF (breakthrough and non-breakthrough cases) will be enrolled. The investigators will collect clinical data, serum cardiac biomarkers and echocardiographic indices of the LA and LAA. All patients will receive standardized annual follow-ups until the end of the study, defined as 12 months after the inclusion of the last participant. The primary endpoint is ischemic stroke or systemic embolism during follow-up. First, in a cross-sectional design, the study will assess the association between serum cardiac biomarkers and echocardiographic indices among patients with breakthrough vs. non-breakthrough stroke as index event, applying multivariate regression models. Second, the investigators will perform a longitudinal analysis assessing the association between the variables mentioned above and breakthrough stroke as index event with the primary endpoint, using multivariate Cox regression models. The study aims to enroll a minimum of 500 patients, which provides sufficient power to detect a clinically meaningful adjusted hazard ratio for recurrent stroke of 1.5 with 80% power at an alpha level of 5%.
Conclusion
The results of this project will enhance understanding of the role of specific clinical factors, cardiac serum biomarkers and echocardiographic indices in the residual risk of stroke in patients with AF on anticoagulation therapy. They may improve current risk stratification and have the potential to help guide therapeutic decisions in high-risk situations considering evolving therapeutic possibilities.
40 studies on the registry are indexed under Embolic Stroke; 11 are open to participants now.
This study's planned enrollment of 500 is above the median of 364 across 27 observational studies indexed under Embolic Stroke.
Browse Embolic Stroke studies →Insel Gruppe AG, University Hospital Bern is the lead sponsor of 741 studies on the registry; 180 are open to participants now.
Compared within Embolic Stroke, this study's primary condition as ClinicalTrials.gg classifies it; the registry's first condition term is Ischemic Stroke. The counts are of registry records indexed under each term, refreshed daily. How we classify →
All patients with ischemic stroke and atrial fibrillation that are admitted to the stroke center of the Inselspital, University Hospital Bern, Switzerland.
Atrial fibrillation may be known prior to the index stroke or newly diagnosed and patients may be anticoagulated or not.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Life expectancy
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
No intervention
Composite of recurrent ischemic stroke or systemic embolism
* Ischemic stroke defined as new neurological symptoms lasting \>24h and/or evidence of new ischemic lesions in neuroimaging (CT and/or MRI) * Systemic embolism, defined as an abrupt vascular insufficiency associated with radiological evidence of arterial occlusion of an extremity or internal organ, in absence of any other, more-likely etiology (e.g. trauma) * Will be assessed through structured telephone visits at every follow-up visit
Time frame: Assessed in first follow-up visit at 12 months (+/- 30 days) after enrolment. Subsequent assessments/visits will be every 12 months and at the end of study (if last visit has taken place >90days prior). Minimal Follow up per patient is 12 months.
All-cause death
Death of all cause \- Will be assessed through structured telephone visits at every follow-up visit
Time frame: Assessed in first follow-up visit at 12 months (+/- 30 days) after enrolment. Subsequent assessments/visits will be every 12 months and at the end of study (if last visit has taken place >90days prior). Minimal Follow up per patient is 12 months.
MACE (major adverse cardial events), defined as a composite outcome of myocardial infarction (MI), ischemic and haemorrhagic stroke, transient ischemic attack (TIA), systemic embolism and cardiovascular death
* Myocardial infarction, defined according to the 4th Universal Definition of MI as a combination of acute myocardial injury (changes in cardiac biomarkers) and evidence of acute myocardial ischemia derived from the clinical presentation, electrocardiographic changes, or the results of myocardial or coronary artery imaging.25 * Transient ischemic attack, defined as a transient episode of neurologic dysfunction caused by focal ischemia (brain, spinal cord or retina) not fulfilling stroke-criteria * Intracranial haemorrhage, defined as intracranial haemorrhage (intraparenchymal, subarachnoid, sub-/epidural) not due to trauma * Cardiovascular death, resulting from cardio-/cerebrovascular causes (e.g. myocardial infarction, sudden cardiac or unwitnessed death, stroke etc. * Will be assessed through structured telephone visits at every follow-up visit
Time frame: Assessed in first follow-up visit at 12 months (+/- 30 days) after enrolment. Subsequent assessments/visits will be every 12 months and at the end of study (if last visit has taken place >90days prior). Minimal Follow up per patient is 12 months.
Episodes of symptomatic AF
Defined as symptoms attributable to AF that led to change in medication (initiation and/or change of rhythm and/or rate control medication), AF-ablation and / or electro-conversion. \- Will be assessed through structured telephone visits at every follow-up visit
Time frame: Assessed in first follow-up visit at 12 months (+/- 30 days) after enrolment. Subsequent assessments/visits will be every 12 months and at the end of study (if last visit has taken place >90days prior). Minimal Follow up per patient is 12 months.
Functional outcome: modified Rankin Scale
Functional outcome measured using the modified Rankin Scale (mRS), ranging from 0 (no symptoms) to 6 (death) \- Will be assessed through structured telephone visits at every follow-up visit
Time frame: Assessed in first follow-up visit at 12 months (+/- 30 days) after enrolment. Subsequent assessments/visits will be every 12 months and at the end of study (if last visit has taken place >90days prior). Minimal Follow up per patient is 12 months.
Functional outcome: Quality of life
Functional outcome measured as subjective quality of life with EQ5D-Score (EuroQol-5 dimensions score) * Assesses overall quality of life with a score ranging from 0 (worst) to 100 (best) * Assesses 5 dimensions of daily live, each ranging from 0 (no problem) to 5 (severe problem): Mobility, Self-Care, Activities of daily life, pain and discomfort, anxiety and depression * Will be assessed through structured telephone visits at every follow-up visit
Time frame: Assessed in first follow-up visit at 12 months (+/- 30 days) after enrolment. Subsequent assessments/visits will be every 12 months and at the end of study (if last visit has taken place >90days prior). Minimal Follow up per patient is 12 months.
Plan to share: No
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Insel Gruppe AG, University Hospital Bern →