Early treatment of Atrial fibrillation for Stroke prevention Trial in acute STROKE (EAST-STROKE): protocol for an international investigator-initiated, prospective, randomised, open, blinded endpoint assessment (PROBE) interventional multi-centre trial

BACKGROUND: Acute ischaemic stroke patients with atrial fibrillation (AF) are at high risk of suffering a recurrent stroke or other cardiovascular complications. It is uncertain whether early rhythm-control therapy is effective and safe in preventing recurrent strokes and cardiovascular complications in these patients. STUDY DESIGN: Early treatment of Atrial fibrillation for Stroke prevention Trial in acute STROKE (EAST-STROKE) is an international investigator-initiated, prospective, randomised, open, blinded endpoint assessment (PROBE) interventional multi-centre trial. Patients with acute ischaemic stroke and AF will be randomised within 4 weeks of stroke (1:1) to receive either early rhythm control and usual care or usual care alone. Usual care includes oral anticoagulation, rate control and treatment of cardiovascular conditions. Early rhythm control additionally comprises treatment with antiarrhythmic drugs, AF ablation or cardioversion. A minimum of 1746 participants will be randomised to observe 351 events. The adaptive design includes one interim analysis with sample size re-estimation after 50% of events. STUDY ENDPOINTS: The primary outcome is a composite of first recurrent ischaemic stroke, haemorrhagic stroke, unclassified stroke, cardiovascular death or hospitalisation due to worsening of heart failure or due to acute coronary syndrome, analysed as time to the first occurrence. Secondary outcomes include individual components of the primary outcome, functional status and patient-reported outcome measures. Safety outcomes comprise all-cause mortality and adverse events. Patients will be followed-up until the end of the trial with a minimum follow-up period of 24 months and an expected mean follow-up period of 42 months. SUMMARY: EAST-STROKE will determine whether early rhythm-control therapy in addition to usual care is effective and safe in patients with acute ischaemic stroke and AF. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05293080; EUCT-No.: 2025-521260-35-00.