Early Treatment of Atrial Fibrillation for Stroke Prevention Trial in Acute STROKE

Study Overview
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Brief Summary
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This study will determine whether early, comprehensive, rhythm control therapy prevents adverse cardiovascular outcome in patients with acute ischemic stroke and atrial fibrillation compared to usual care.

Detailed Description
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trial fibrillation is the single most frequent cause of ischemic stroke and associated with a high risk of recurrent stroke and cardiovascular complications. Usual care comprises oral anticoagulation and rate control. However, it is unclear, whether early rhythm control therapy reduces the risk of recurrent stroke and cardiovascular outcomes in stroke patients with atrial fibrillation. The Early treatment of Atrial fibrillation for Stroke prevention Trial in acute STROKE (EAST-STROKE) will be an investigator-initiated, prospective, randomized, open, blinded outcome assessment (PROBE) interventional multi-center trial to test whether early, comprehensive, rhythm control therapy prevents adverse cardiovascular outcome in patients with acute ischemic stroke and atrial fibrillation compared to usual care. Primary outcome is a composite of recurrent stroke, cardiovascular death, and hospitalization due to worsening of heart failure or acute coronary syndrome. Secondary outcomes will involve a comprehensive array of clinical and safety parameters, health and socio-economic outcomes including patient reported outcome measures. In an adaptive design, up to 1,746 patients will be enrolled to demonstrate the expected treatment effect with 90% power.

Official Title
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Early Treatment of Atrial Fibrillation for Stroke Prevention Trial in Acute STROKE

Conditions
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Acute Ischemic Stroke, Atrial Fibrillation

Intervention / Treatment
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* Other: Medical or interventional therapy for rhythm control in atrial fibrillation (antiarrhythmic drugs, ablation, electric cardio version)
* Other: Usual care for atrial fibrillation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Acute ischemic stroke in the previous four weeks, diagnosed by imaging (CT or MRI) or clinical diagnosis Possibility to start the trial treatment within 4 weeks after stroke, and as soon as clinically justifiable AF first detected ≤1 year prior to randomization Informed consent Exclusion Criteria: End-stage cancer or life-expectancy < 12 months due to other advanced co-morbid illness Prior AF ablation or surgical therapy of AF Patients not suitable for rhythm control of AF due to cardiac conditions

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Early rhythm control therapy<br>Patients with acute ischemic stroke and AF will receive either catheter ablation (mainly pulmonary vein isolation), or adequate antiarrhythmic drug therapy at an early time point. The initial therapy will be selected by the local investigator. In case of continuation or recurrence of AF, both modalities may be combined. | Other: Medical or interventional therapy for rhythm control in atrial fibrillation (antiarrhythmic drugs, ablation, electric cardio version)<br>* Therapy for early rhythm control will be either by use of approved antiarrhythmic drugs (e.g. amiodarone, dronedarone, flecainide, propafenone), approved approaches and devices for ablation, or electric cardio version.<br>|
| Active Comparator: Usual care<br>Patients with acute ischemic stroke and AF will receive usual care following the current ESC guidelines for AF treatment. | Other: Usual care for atrial fibrillation<br>* Usual care for atrial fibrillation according to current guidelines. Usual care will mainly comprise rate control by approved drugs. We expect, that usual care will also comprise therapy for rhythm control in a small group of patients.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to first recurrent stroke, cardiovascular death, or hospitalization due to worsening of heart failure or due to acute coronary syndrome. | The primary outcome measure is a composite of first recurrent stroke, cardiovascular death, and hospitalization due to worsening of heart failure or due to acute coronary syndrome as recorded by study investigators | Through study completion, an average of 42 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to first recurrent stroke | Recurrent stroke as recorded by study investigators | Through study completion, an average of 42 months | 
| Time to cardiovascular death |  | Through study completion, an average of 42 months | 
| Time to first hospitalization due to worsening of heart failure | Hospitalization due to worsening of heart failure as recorded by study investigators | Through study completion, an average of 42 months | 
| Time to hospitalization due to acute coronary syndrome | Hospitalization due to acute coronary syndrome as recorded by study investigators | Through study completion, an average of 42 months | 
| Time to recurrent AF |  | Through study completion, an average of 42 months | 
| Cardiovascular hospitalization | Cardiovascular hospitalization as recorded by study investigators | Through study completion, an average of 42 months | 
| All-cause hospitalizations | All-cause hospitalizations as recorded by study investigators | Through study completion, an average of 42 months | 
| Time in sinus rhythm |  | Through study completion, an average of 42 months | 
| Functional status assessed by the modified Rankin Scale | Modified Ranking Scale ranging from 0 (no symptoms) to 6 (death) with lower values indicating better status | at 12 and 24 months | 
| Quality of life assessed by the EuroQol five-dimensional questionnaire (EQ-5D) | The EQ-5D index will be calculated with higher values indicating better health state | at 12 and 24 months | 
| Cognitive function assessed by the Montreal Cognitive Assessment (MoCA) | The MoCA ranges for 0 to 30, with higher values indicating better cognitive function | at 12 and 24 months | 
| Cost of therapy |  | Through study completion, an average of 42 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute ischemic stroke, Atrial fibrillation, Rhythm control, Ablation, Antiarrhythmic drugs