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

• ClinicalTrials.gov Identifier: NCT04371055
• Recruitment Status: Recruiting
• First Posted: May 1, 2020
• Last Update Posted: April 3, 2024
• Sponsor: University of Leipzig
• Collaborator: Johannes Gutenberg University Mainz
• Information provided by (Responsible Party): Rolf Wachter, University of Leipzig

Tracking Information

• First Submitted Date: April 24, 2020
• First Posted Date: May 1, 2020
• Last Update Posted Date: April 3, 2024
• Actual Study Start Date: July 7, 2020
• Estimated Primary Completion Date: June 30, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 30, 2020)

• Primary efficacy endpoint: Time until recurrent ischemic stroke or systemic embolism [ Time Frame: 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 [ Time Frame: from the date of randomization until the date of first documented haemorrhagic stroke, assessed up to 60 months ]
  Time until the first haemorrhagic stroke

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 30, 2020)

• Time until the combination of stroke, myocardial infarction and cardiovascular death [ Time Frame: 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 any stroke [ Time Frame: from the date of randomization until the date of first documented any stroke, assessed up to 60 months ]
  Time until any stroke
• Time until new onset of AF [ Time Frame: from the date of randomization until the date of first documented AF, assessed up to 60 months ]
  Time until new onset of Atrial Fibrillation
• Time until all cause mortality [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 overall QoL visual analog scale [ Time Frame: 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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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

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 Type: Interventional
• Study Phase: Not Applicable

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Randomised, parallel, multicenter interventional trial with blinded assessment of the primary endpoint

Masking: Single (Outcomes Assessor)
Primary Purpose: Prevention

Condition

• Ischemic Stroke
• Atrial Fibrillation

Intervention

• 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
  Usual care according to current guidelines (in patients with low and high risk of atrial fibrillation)

Study Arms

• 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

  Interventions:

  • Other: 7-day Holter ECG
  • Other: Implantable cardiac monitor
• Standard of Care
  Standard of care rhythm monitoring
  Intervention: Other: Standard of care

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 30, 2020): 5200
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 31, 2026
• Estimated Primary Completion Date: June 30, 2026 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 60 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Rolf Wachter, Prof. Dr.; +49-341-97-12650; rolf.wachter@medizin.uni-leipzig.de

Contact: Katrin Wasser, PD Dr. med.; +49-551-3920-194; k.wasser@med.uni-goettingen.de

• Listed Location Countries: Germany

Administrative Information

• NCT Number: NCT04371055
• Other Study ID Numbers: Find-AF 2
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Time Frame: after publication of the major results

• Current Responsible Party: Rolf Wachter, University of Leipzig
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Leipzig
• Original Study Sponsor: Same as current
• 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

• PRS Account: University of Leipzig
• Verification Date: April 2024