Early Treatment of Atrial Fibrillation for Stroke Prevention Trial in Acute STROKE (EAST-STROKE)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Atrial Fibrillation; Acute Ischemic Stroke
• Intervention / Treatment: Other: Medical or interventional therapy for rhythm control in atrial fibrillation (antiarrhythmic drugs, ablation, electric cardio version); Other: Usual care for atrial fibrillation

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 1746
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Märit Jensen, MD; Phone Number: +4940741053770; Email: m.jensen@uke.de
• Study Contact Backup: Name: Götz Thomalla, MD; Phone Number: +4940741050137; Email: thomalla@uke.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

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: Early rhythm control therapy; 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); 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.
Active Comparator: Usual care; 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; 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.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause mortality	Death from any cause	Through study completion, an average of 42 months
Severe bleeding complications	Intracranial hemorrhage, major bleeding	Through study completion, an average of 42 months
Adverse events	Adverse events related to the study intervention with special emphasis on proarrhythmia and complications due to interventions	Through study completion, an average of 42 months

Collaborators and Investigators

• Sponsor: Universitätsklinikum Hamburg-Eppendorf
• Collaborators: UMC Utrecht; Hotchkiss Brain Institute, University of Calgary; Kompetenznetz Vorhofflimmern e.V. (AFNET); University Heart & Vascular Center Hamburg, Department of Cardiology; Department of Neurology, Royal Melbourne Hospital; Melbourne Heart Centre, Royal Melbourne Hospital; Department of Neurology and Neurosurgery, Brain Center, University Medical Center Utrecht; Edinburgh Clinical Trials Unit, Cerebrovascular Research Group, Centre for Clinical Brain Sciences, University of Edinburgh; Department of Cardiovascular Sciences, University of Leicester British Heart Foundation Cardiovascular Research Centre; Institute of Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf; CTC-NORTH; Stroke Alliance for Europe (SAFE)
• Investigators: Principal Investigator: Götz Thomalla, MD, Universitatsklinikum Hamburg-Eppendorf

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2024
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): March 1, 2029

Study Registration Dates

• First Submitted: March 1, 2022
• First Submitted That Met QC Criteria: March 14, 2022
• First Posted (Actual): March 24, 2022

Study Record Updates

• Last Update Posted (Actual): December 28, 2023
• Last Update Submitted That Met QC Criteria: December 27, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Atrial fibrillation; Ablation; Acute ischemic stroke; Rhythm control; Antiarrhythmic drugs
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Arrhythmias, Cardiac; Stroke; Ischemic Stroke; Atrial Fibrillation; Anti-Arrhythmia Agents
• Other Study ID Numbers: EAST-STROKE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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