Intensive Rhythm Monitoring to Decrease Ischemic Stroke and Systemic Embolism - the Find-AF 2 Study (Find-AF2)

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Ischemic Stroke; Atrial Fibrillation
• Intervention / Treatment: Other: 7-day Holter ECG; Other: Implantable cardiac monitor; Other: Standard of care

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 Type: Interventional
• Enrollment (Actual): 5227
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Altenburg, Germany
    • Klinikum Altenburger Land
  • Aschaffenburg, Germany
    • Klinikum Aschaffenburg-Alzenau
  • Augsburg, Germany
    • Universitätsklinikum Augsburg
  • Bad Neustadt An Der Saale, Germany
    • Rhön Klinikum Campus Bad Neustadt
  • Bamberg, Germany
    • Sozialstiftung Bamberg; Klinikum am Bruderwald
  • Berlin, Germany
    • BG Klinikum, Unfall-KH Berlin gGmbH
  • Berlin, Germany
    • Vivantes Klinikum Neukölln Berlin
  • Berlin, Germany
    • Vivantes, Humboldt-Klinikum Berlin
  • Berlin-Spandau, Germany
    • Vivantes Klinikum Spandau
  • Bielefeld, Germany, 33611
    • Evangelisches Klinikum Bethel, Klinik für Neurologie
  • Bonn, Germany
    • Universitätsklinikum Bonn
  • Bremen, Germany
    • Klinikum Bremen Mitte
  • Coburg, Germany, 96450
    • Klinikum Coburg, Medizinische Klinik für Innere Medizin und Kardiologie
  • Darmstadt, Germany
    • Klinikum Darmstadt
  • Dresden, Germany
    • Universitatsklinikum Carl Gustav Carus
  • Dresden, Germany
    • Städtisches Klinikum Dresden, Standort Friedrichstadt
  • Erlangen, Germany
    • Universitätsklinikum Erlangen
  • Essen, Germany, 45147
    • University of Essen, Clinic for Neurology
  • Frankfurt, Germany
    • Klinikum Frankfurt Höchst
  • Frankfurt, Germany
    • Universitätsklinikum Frankfurt
  • Fulda, Germany
    • Klinikum Fulda
  • Gießen, Germany
    • Universitätsklinikum Gießen und Marburg GmbH
  • Göttingen, Germany, 37075
    • University of Göttingen, Clinic for Neurology
  • Günzburg, Germany
    • Bezirkskrankenhaus Günzburg
  • Halle, Germany
    • Krankenhaus Martha-Maria Halle-Dölau
  • Hamburg, Germany
    • Universitätsklinikum Hamburg-Eppendorf
  • Hamburg, Germany
    • Albertinenkrankenhaus Hamburg
  • Hamburg, Germany
    • Asklepios Klinik Altona Hamburg
  • Hamburg, Germany
    • Asklepios Klinik Wandsbek, Hamburg
  • Hannover, Germany
    • Medizinische Hochschule Hannover
  • Heidelberg, Germany
    • Universitatsklinikum Heidelberg
  • Höxter, Germany
    • Klinikum Höxter
  • Ibbenbüren, Germany
    • Klinikum Ibbenbüren
  • Leipzig, Germany
    • Klinikum St. Georg Leipzig
  • Lüneburg, Germany
    • Städtisches Klinikum Lüneburg gemeinnützige GmbH
  • Mainz, Germany, 55131
    • University of Mainz, Clinic for Neurology
  • Merseburg, Germany
    • Carl-von-Basedow Klinikum Merseburg
  • Minden, Germany
    • Klinikum Minden
  • Mühlhausen, Germany
    • Ökumenisches Hainich Klinikum Mühlhausen
  • Münster, Germany
    • Universitätsklinikum Münster
  • Osnabrück, Germany
    • Klinikum Osnabrück GmbH
  • Passau, Germany
    • Klinikum Passau
  • Sande, Germany, 26452
    • Nordwest-Krankenhaus Sanderbusch, Klinik für Neurologie
  • Siegen, Germany
    • Kreisklinikum Siegen
  • Traunstein, Germany
    • Kliniken Südostbayern AG, Klinikum Traunstein
  • Tübingen, Germany
    • Universitätsklinikum Tübingen
  • Ulm, Germany
    • Universitätsklinikum Ulm
  • Wiesbaden, Germany
    • Helios Dr. Horst Schmidt-Kliniken Wiesbaden
  • Würzburg, Germany
    • Universitatsklinikum Wurzburg
  • Bayern
    • München, Bayern, Germany
      • ISD München
    • Nürnberg, Bayern, Germany, 90471
      • Klinikum Nürnberg
  • Saxony
    • Leipzig, Saxony, Germany, 04103
      • University of Leipzig, Clinic for Neurology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Risk-adapted ECG monitoring for atrial fibrillation; 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	Other: 7-day Holter ECG; 7-day Holter ECG at baseline and after 3 and 12 months and then annually until the end of the study or the first (in patients with low risk of atrial fibrillation); Other: Implantable cardiac monitor; Continuous rhythm monitoring using an implantable cardiac monitor
Other: Standard of Care; Standard of care rhythm monitoring	Other: Standard of care; Usual care according to current guidelines (in patients with low and high risk of atrial fibrillation)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary efficacy endpoint: Time until recurrent ischemic stroke or systemic embolism	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.	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
Primary safety endpoint: Time until the first haemorrhagic stroke	Time until the first haemorrhagic stroke	from the date of randomization until the date of first documented haemorrhagic stroke, assessed up to 60 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time until the combination of stroke, myocardial infarction and cardiovascular death	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 any stroke	Time until any stroke	from the date of randomization until the date of first documented any stroke, assessed up to 60 months
Time until new onset of AF	Time until new onset of Atrial Fibrillation	from the date of randomization until the date of first documented AF, assessed up to 60 months
Time until all cause mortality	Time until all cause mortality	from the date of randomization until the date of all cause mortality assessed up to 60 months
Time until myocardial infarction	Time until myocardial infarction	from the date of randomization until the date of all myocardial infarction, assessed up to 60 months
Changes in quality of life (QoL), measured by the stroke impact scale (SIS-16)	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.	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)	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 overall QoL visual analog scale	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

Collaborators and Investigators

• Sponsor: University of Leipzig
• Collaborators: Johannes Gutenberg University Mainz
• Investigators: Study Chair: Rolf Wachter, Prof. Dr., University of Leipzig, Clinic and Policlinis for Cardiology; Principal Investigator: Klaus Gröschel, Prof. Dr., University of Mainz, Clinic and Policlinis for Neurology

Publications and helpful links

General Publications

• Uhe T, Wasser K, Weber-Kruger M, Schabitz WR, Kohrmann M, Brachmann J, Laufs U, Dichgans M, Gelbrich G, Petroff D, Prettin C, Michalski D, Kraft A, Etgen T, Schellinger PD, Soda H, Bethke F, Ertl M, Kallmunzer B, Grond M, Althaus K, Hamann GF, Mende M, Wagner M, Groschel S, Uphaus T, Groschel K, Wachter R; Find-AF 2 study group. Intensive heart rhythm monitoring to decrease ischemic stroke and systemic embolism-the Find-AF 2 study-rationale and design. Am Heart J. 2023 Nov;265:66-76. doi: 10.1016/j.ahj.2023.06.016. Epub 2023 Jul 7.

Helpful Links

• Study homepage with information for medical experts and the general public

Study record dates

Study Major Dates

• Study Start (Actual): July 7, 2020
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: April 24, 2020
• First Submitted That Met QC Criteria: April 30, 2020
• First Posted (Actual): May 1, 2020

Study Record Updates

• Last Update Posted (Actual): June 4, 2025
• Last Update Submitted That Met QC Criteria: May 29, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Atrial Fibrillation; Ischemic Stroke; Secondary Prevention; ECG Monitoring
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Arrhythmias, Cardiac; Brain Infarction; Brain Ischemia; Infarction; Necrosis; Embolism and Thrombosis; Ischemic Stroke; Stroke; Cerebral Infarction; Ischemia; Atrial Fibrillation; Embolism
• Other Study ID Numbers: Find-AF 2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Time Frame: after publication of the major results
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No