Design and Rationale of the RELAXED (Recurrent Embolism Lessened by rivaroxaban, an Anti-Xa agent, of Early Dosing for acute ischemic stroke and transient ischemic attack with atrial fibrillation) Study.

Background: In the acute phase of cardioembolic stroke in patients with nonvalvular atrial fibrillation (NVAF), the recurrence rate is high. Nonvitamin K antagonist oral anticoagulants may be appropriate for prevention of early recurrence because they have a much lower risk of hemorrhagic stroke than warfarin.

Methods: RELAXED (Recurrent Embolism Lessened by rivaroxaban, an Anti-Xa agent, of Early Dosing for acute ischemic stroke and transient ischemic attack with atrial fibrillation) study is an observational study designed to investigate the optimal timing to start administration of rivaroxaban for prevention of recurrence in NVAF patients in the acute phase of cardioembolic stroke (ClinicalTrials.gov: NCT02129920 and UMIN-clinical trials registry: UMIN000013932). It will evaluate the efficacy and safety of rivaroxaban with regard to infarct size, timing of initiation of rivaroxaban medication, and other patient characteristics. A total of 2000 consecutive patients with acute ischemic stroke in the territory of the middle cerebral artery and NVAF will be enrolled in 100 institutes throughout Japan, and they will receive rivaroxaban within 30 days of the index stroke for secondary prevention of stroke. The infarct size within 48 hours after stroke onset will be measured by diffusion-weighted magnetic resonance imaging. The primary efficacy endpoint is recurrent ischemic stroke, and the primary safety endpoint is major bleeding during the observational period of 3 months after stroke onset. The optimal timing to start treatment with rivaroxaban during the acute stage of ischemic stroke will be determined by analysis of the correlation between primary endpoints and the size of cerebral infarct.

Conclusions: The RELAXED observational registry study will elucidate the optimal timing of the initiation of rivaroxaban in acute cardioembolic stroke associated with NVAF.