Intensive Rhythm Monitoring to Decrease Ischemic Stroke and Systemic Embolism - the Find-AF 2 Study

Not Applicable

Active, not recruiting

• Conditions: Ischemic Stroke; Atrial Fibrillation
• Interventions: Other: 7-day Holter ECG; Other: Standard of care; Other: Implantable cardiac monitor

• Registration Number: NCT04371055
• Lead Sponsor: University of Leipzig

Brief Summary

Patients who have suffered a stroke are having an increased risk of having recurrent stroke in the future. This risk of stroke is increased by atrial fibrillation, which often "comes and goes" (called paroxysmal) and hence escapes routine diagnostics. The hypothesis of Find-AF 2 is that enhanced (evaluation in a ECG core lab), prolonged (at least 7 days of rhythm monitoring annually) and intensified (continuous rhythm monitoring in high risk patients) not only finds atrial fibrillation more often, but that changes in therapeutic management (e. g. start of anticoagulation after detection of atrial fibrillation) results in a decrease of cardioembolism (which can be either recurrent stroke or systemic embolism).

To prove this hypothesis, patients will be randomised into two groups: the first group will receive the currently available standard care for patients with stroke. In the second group, cardiac rhythm monitoring adapted to the risk of the occurrence of atrial fibrillation is performed - either with a 7-day long-term ECG (at baseline, after 3 and 12 months and every 12 months thereafter) or with continuous monitoring using an implantable cardiac monitor. If atrial fibrillation is detected, this information will be given to the treating study physician. Any therapeutic decision is at the discretion of the treating physician, but should follow current guidelines.

Detailed Description

The Find AF 2 study will investigate whether intensified rhythm monitoring in patients with recent ischemic stroke leads to a decrease in recurrent thromboembolism (defined as recurrent ischemic stroke or systemic embolism). This will be achieved by identifying patients with paroxysmal atrial fibrillation and subsequently switching secondary prevention therapy from antiplatelet therapy to oral anticoagulation. The intensity of heart rhythm monitoring will be risk-adjusted: Patients with an estimated low risk of atrial fibrillation receive a 7-day Holter ECG, which is repeated after 3 and 12 months and annually thereafter. Patients with a high risk of atrial fibrillation (defined by increased supraventricular ectopic activity) receive continuous ECG monitoring using an implanted loop recorder. The control arm is treated according to local standards, which includes cardiac rhythm monitoring for at least 24 hours according to current guidelines. Prior to randomization, a 24-hour Holter ECG is performed in both study arms, ensuring minimal ECG monitoring for patients in the control arm and allowing risk stratification in the intervention arm. Additional ECG monitoring using stroke telemetry and/or additional Holter ECGs is possible according to local standards, provided it does not exceed 7 days. Patients in both study arms will be followed up for at least 24 months.

It should be noted that this study only provides diagnostic information, the therapeutic decision is left to the treating physician.

Study Timeline

• Study First Submitted: 2020-04-24
• Study First Submitted QC: 2020-04-30
• Study First Posted: 2020-05-01
• Study Start: 2020-07-07
• Status Verified: 2025-01
• Last Update Submitted: 2025-03-08
• Last Update Posted: 2025-03-12
• Primary Completion: 2026-06-30
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 5229

Inclusion Criteria

1. Recent ischemic stroke (sudden focal neurologic deficit lasting > 24h consistent with the territory of a major cerebral artery) and/or a corresponding lesion on brain imaging within the last 30 days
2. Age ≥ 60 years
3. Patient without or with only slight disability (modified Rankin Scale score ≤ 2) before onset of stroke-related symptoms.
4. Written informed consent

Exclusion Criteria

1. Known history of atrial fibrillation/flutter or atrial fibrillation/flutter on admission ECG
2. Current indication or contraindication for oral anticoagulation at randomisation
3. Intracerebral bleeding in medical history
4. Patient scheduled for ECG-monitoring lasting > 7 days (Holter-ECG, implanted loop recorder, etc.)
5. Implanted pacemaker device or cardioverter/ defibrillator
6. Patient not willing to be treated with oral anticoagulants
7. Carotid artery stenosis ipsilateral to the current ischemic stroke needing operation or intervention.
8. History of carotid endarterectomy or percutaneous intervention of cerebral artery within the last 30 days.
9. Life expectancy <1 year for reasons other than stroke (e.g. metastatic cancer)
10. patients under legal supervision or guardianship
11. psychological/mental or other inabilities to supply required information (e.g. fill out the questionnaire due to dementia, language difficulties,...) or participate in the required tests
12. participation in other randomised interventional trials
13. suspected lack of compliance

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Risk-adapted ECG monitoring for atrial fibrillation	7-day Holter ECG	Intervention Group with high Risk for AF: Continuous Rhythm Monitoring using an implantable cardiac Monitor Intervention group with low risk for AF: 7-day Holter ECG at baseline, after 3 and 12 months and then annually until the end of the study or the first occurrence of atrial Fibrillation
Standard of Care	Standard of care	Standard of care rhythm monitoring
Risk-adapted ECG monitoring for atrial fibrillation	Implantable cardiac monitor	Intervention Group with high Risk for AF: Continuous Rhythm Monitoring using an implantable cardiac Monitor Intervention group with low risk for AF: 7-day Holter ECG at baseline, after 3 and 12 months and then annually until the end of the study or the first occurrence of atrial Fibrillation

Primary Outcome Measures

Name	Time	Method
Primary efficacy endpoint: Time until recurrent ischemic stroke or systemic embolism	from the date of randomization until the date of first documented ischemic stroke or date of first systemic embolism, whichever comes first, assessed up to 60 months	The trial will be event driven. The minimum follow-up in each patient is 24 months, but may be followed for up to 60 months.
Primary safety endpoint: Time until the first haemorrhagic stroke	from the date of randomization until the date of first documented haemorrhagic stroke, assessed up to 60 months	Time until the first haemorrhagic stroke

Secondary Outcome Measures

Name	Time	Method
Time until any stroke	from the date of randomization until the date of first documented any stroke, assessed up to 60 months	Time until any stroke
Time until all cause mortality	from the date of randomization until the date of all cause mortality assessed up to 60 months	Time until all cause mortality
Time until myocardial infarction	from the date of randomization until the date of all myocardial infarction, assessed up to 60 months	Time until myocardial infarction
Changes in quality of life (QoL), measured by the stroke impact scale (SIS-16)	Mean change from baseline until study end assessed up to 60 months in both study arms	Changes in quality of life (QoL), measured by the stroke impact scale (SIS-16). The SIS-16 ranges from 16 to 80, with higher scores showing better Quality of life.
Changes in the EQ-5D five dimensional Quality of Life (QoL)	Mean change from baseline until study end assessed up to 60 months in both study arms	Changes in the EQ-5D five dimensional Quality of Life (QoL)
Time until the combination of stroke, myocardial infarction and cardiovascular death	from the date of randomization until the date of first documented stroke, the date of myocardial infarction and the date of cardiovascular death, whichever comes first, assessed up to 60 months	Time until the combination of stroke, myocardial infarction and cardiovascular death
Time until new onset of AF	from the date of randomization until the date of first documented AF, assessed up to 60 months	Time until new onset of Atrial Fibrillation
Changes in the overall QoL visual analog scale	Mean change from baseline until study end assessed up to 60 months in both study arms, ranging from 0 to 100, with higher values indicating better quality of life	Changes in the overall QoL visual analog scale

Trial Locations

Locations (52)

ISD München; 🇩🇪 München, Bayern, Germany

Klinikum Nürnberg; 🇩🇪 Nürnberg, Bayern, Germany

University of Leipzig, Clinic for Neurology; 🇩🇪 Leipzig, Saxony, Germany

Klinikum Altenburger Land; 🇩🇪 Altenburg, Germany

Klinikum Aschaffenburg-Alzenau; 🇩🇪 Aschaffenburg, Germany

Universitätsklinikum Augsburg; 🇩🇪 Augsburg, Germany

Rhön Klinikum Campus Bad Neustadt; 🇩🇪 Bad Neustadt An Der Saale, Germany

Sozialstiftung Bamberg; Klinikum am Bruderwald; 🇩🇪 Bamberg, Germany

Vivantes Klinikum Spandau; 🇩🇪 Berlin-Spandau, Germany

BG Klinikum, Unfall-KH Berlin gGmbH; 🇩🇪 Berlin, Germany

Vivantes Klinikum Neukölln Berlin; 🇩🇪 Berlin, Germany

Vivantes, Humboldt-Klinikum Berlin; 🇩🇪 Berlin, Germany

Evangelisches Klinikum Bethel, Klinik für Neurologie; 🇩🇪 Bielefeld, Germany

Universitätsklinikum Bonn; 🇩🇪 Bonn, Germany

Klinikum Bremen Mitte; 🇩🇪 Bremen, Germany

Klinikum Coburg, Medizinische Klinik für Innere Medizin und Kardiologie; 🇩🇪 Coburg, Germany

Klinikum Darmstadt; 🇩🇪 Darmstadt, Germany

Städtisches Klinikum Dresden, Standort Friedrichstadt; 🇩🇪 Dresden, Germany

Universitätsklinikum Carl Gustav Carus; 🇩🇪 Dresden, Germany

Universitätsklinikum Erlangen; 🇩🇪 Erlangen, Germany

University of Essen, Clinic for Neurology; 🇩🇪 Essen, Germany

Klinikum Frankfurt Höchst; 🇩🇪 Frankfurt, Germany

Universitätsklinikum Frankfurt; 🇩🇪 Frankfurt, Germany

Klinikum Fulda; 🇩🇪 Fulda, Germany

Universitätsklinikum Gießen und Marburg GmbH; 🇩🇪 Gießen, Germany

University of Göttingen, Clinic for Neurology; 🇩🇪 Göttingen, Germany

Bezirkskrankenhaus Günzburg; 🇩🇪 Günzburg, Germany

Krankenhaus Martha-Maria Halle-Dölau; 🇩🇪 Halle, Germany

Albertinenkrankenhaus Hamburg; 🇩🇪 Hamburg, Germany

Asklepios Klinik Altona Hamburg; 🇩🇪 Hamburg, Germany

Asklepios Klinik Wandsbek, Hamburg; 🇩🇪 Hamburg, Germany

Universitätsklinikum Hamburg-Eppendorf; 🇩🇪 Hamburg, Germany

Medizinische Hochschule Hannover; 🇩🇪 Hannover, Germany

University of Mainz, Clinic for Neurology; 🇩🇪 Mainz, Germany

Universitätsklinikum Heidelberg; 🇩🇪 Heidelberg, Germany

Klinikum Höxter; 🇩🇪 Höxter, Germany

Klinikum Ibbenbüren; 🇩🇪 Ibbenbüren, Germany

Klinikum St. Georg Leipzig; 🇩🇪 Leipzig, Germany

Carl-von-Basedow Klinikum Merseburg; 🇩🇪 Merseburg, Germany

Klinikum Minden; 🇩🇪 Minden, Germany

Ökumenisches Hainich Klinikum Mühlhausen; 🇩🇪 Mühlhausen, Germany

Universitätsklinikum Münster; 🇩🇪 Münster, Germany

Klinikum Osnabrück GmbH; 🇩🇪 Osnabrück, Germany

Klinikum Passau; 🇩🇪 Passau, Germany

Städtisches Klinikum Lüneburg gemeinnützige GmbH; 🇩🇪 Lüneburg, Germany

Nordwest-Krankenhaus Sanderbusch, Klinik für Neurologie; 🇩🇪 Sande, Germany

Kreisklinikum Siegen; 🇩🇪 Siegen, Germany

Kliniken Südostbayern AG, Klinikum Traunstein; 🇩🇪 Traunstein, Germany

Universitätsklinikum Tübingen; 🇩🇪 Tübingen, Germany

Universitätsklinikum Ulm; 🇩🇪 Ulm, Germany

Helios Dr. Horst Schmidt-Kliniken Wiesbaden; 🇩🇪 Wiesbaden, Germany

Universitätsklinikum Würzburg; 🇩🇪 Würzburg, Germany