Clinical trial NCT04371055: Intensive Rhythm Monitoring to Decrease Ischemic Stroke and Systemic Embolism - the Find-AF 2 Study
Official title: Intensive Heart Rhythm Monitoring to Decrease Ischemic Stroke and Systemic Embolism - the Find-AF 2 Study
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Ischemic Stroke
Atrial Fibrillation
Keywords: Atrial Fibrillation
Ischemic Stroke
ECG Monitoring
Secondary Prevention
Lead sponsor: University of Leipzig
Sponsor class: OTHER
Collaborators: name: Johannes Gutenberg University Mainz
First posted: 2020-05-01
Enrollment: 5227
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomised, parallel, multicenter interventional trial with blinded assessment of the primary endpoint
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Primary efficacy endpoint: Time until recurrent ischemic stroke or systemic embolism
timeFrame: 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
measure: Primary safety endpoint: Time until the first haemorrhagic stroke
timeFrame: from the date of randomization until the date of first documented haemorrhagic stroke, assessed up to 60 months
Secondary outcomes:
measure: Time until the combination of stroke, myocardial infarction and cardiovascular death
timeFrame: 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
measure: Time until any stroke
timeFrame: from the date of randomization until the date of first documented any stroke, assessed up to 60 months
measure: Time until new onset of AF
timeFrame: from the date of randomization until the date of first documented AF, assessed up to 60 months
measure: Time until all cause mortality
timeFrame: from the date of randomization until the date of all cause mortality assessed up to 60 months
measure: Time until myocardial infarction
timeFrame: from the date of randomization until the date of all myocardial infarction, assessed up to 60 months
measure: Changes in quality of life (QoL), measured by the stroke impact scale (SIS-16)
timeFrame: Mean change from baseline until study end assessed up to 60 months in both study arms
measure: Changes in the EQ-5D five dimensional Quality of Life (QoL)
timeFrame: Mean change from baseline until study end assessed up to 60 months in both study arms
measure: Changes in the overall QoL visual analog scale
timeFrame: 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
Other outcomes:
Locations:
city: München
country: Germany
facility: ISD München
state: Bayern
city: Nürnberg
country: Germany
facility: Klinikum Nürnberg
state: Bayern
city: Leipzig
country: Germany
facility: University of Leipzig, Clinic for Neurology
state: Saxony
city: Altenburg
country: Germany
facility: Klinikum Altenburger Land
city: Aschaffenburg
country: Germany
facility: Klinikum Aschaffenburg-Alzenau
city: Augsburg
country: Germany
facility: Universitätsklinikum Augsburg
city: Bad Neustadt An Der Saale
country: Germany
facility: Rhön Klinikum Campus Bad Neustadt
city: Bamberg
country: Germany
facility: Sozialstiftung Bamberg; Klinikum am Bruderwald
city: Berlin-Spandau
country: Germany
facility: Vivantes Klinikum Spandau
city: Berlin
country: Germany
facility: BG Klinikum, Unfall-KH Berlin gGmbH
city: Berlin
country: Germany
facility: Vivantes Klinikum Neukölln Berlin
city: Berlin
country: Germany
facility: Vivantes, Humboldt-Klinikum Berlin
city: Bielefeld
country: Germany
facility: Evangelisches Klinikum Bethel, Klinik für Neurologie
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn
city: Bremen
country: Germany
facility: Klinikum Bremen Mitte
city: Coburg
country: Germany
facility: Klinikum Coburg, Medizinische Klinik für Innere Medizin und Kardiologie
city: Darmstadt
country: Germany
facility: Klinikum Darmstadt
city: Dresden
country: Germany
facility: Städtisches Klinikum Dresden, Standort Friedrichstadt
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus
city: Erlangen
country: Germany
facility: Universitätsklinikum Erlangen
city: Essen
country: Germany
facility: University of Essen, Clinic for Neurology
city: Frankfurt
country: Germany
facility: Klinikum Frankfurt Höchst
city: Frankfurt
country: Germany
facility: Universitätsklinikum Frankfurt
city: Fulda
country: Germany
facility: Klinikum Fulda
city: Gießen
country: Germany
facility: Universitätsklinikum Gießen und Marburg GmbH
city: Göttingen
country: Germany
facility: University of Göttingen, Clinic for Neurology
city: Günzburg
country: Germany
facility: Bezirkskrankenhaus Günzburg
city: Halle
country: Germany
facility: Krankenhaus Martha-Maria Halle-Dölau
city: Hamburg
country: Germany
facility: Albertinenkrankenhaus Hamburg
city: Hamburg
country: Germany
facility: Asklepios Klinik Altona Hamburg
city: Hamburg
country: Germany
facility: Asklepios Klinik Wandsbek, Hamburg
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg
city: Höxter
country: Germany
facility: Klinikum Höxter
city: Ibbenbüren
country: Germany
facility: Klinikum Ibbenbüren
city: Leipzig
country: Germany
facility: Klinikum St. Georg Leipzig
city: Lüneburg
country: Germany
facility: Städtisches Klinikum Lüneburg gemeinnützige GmbH
city: Mainz
country: Germany
facility: University of Mainz, Clinic for Neurology
city: Merseburg
country: Germany
facility: Carl-von-Basedow Klinikum Merseburg
city: Minden
country: Germany
facility: Klinikum Minden
city: Mühlhausen
country: Germany
facility: Ökumenisches Hainich Klinikum Mühlhausen
city: Münster
country: Germany
facility: Universitätsklinikum Münster
city: Osnabrück
country: Germany
facility: Klinikum Osnabrück GmbH
city: Passau
country: Germany
facility: Klinikum Passau
city: Sande
country: Germany
facility: Nordwest-Krankenhaus Sanderbusch, Klinik für Neurologie
city: Siegen
country: Germany
facility: Kreisklinikum Siegen
city: Traunstein
country: Germany
facility: Kliniken Südostbayern AG, Klinikum Traunstein
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm
city: Wiesbaden
country: Germany
facility: Helios Dr. Horst Schmidt-Kliniken Wiesbaden
city: Würzburg
country: Germany
facility: Universitätsklinikum Würzburg
Study officials:
affiliation: University of Leipzig, Clinic and Policlinis for Cardiology
name: Rolf Wachter, Prof. Dr.
role: STUDY_CHAIR
affiliation: University of Mainz, Clinic and Policlinis for Neurology
name: Klaus Gröschel, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.