Lixiana Acute Stroke Evaluation Registry

Study Hypothesis:

Investigators hypothesize that edoxaban initiation within five days of ischemic stroke will not be associated with increased HT rates, relative to patients in whom anticoagulation is delayed. Serial imaging using CT will be utilized to determine the rate of radiological HT after edoxaban initiation. Incident radiological HT rates will be assessed as objective performance criteria for the safety of early versus delayed edoxaban initiation. Investigators also hypothesize that RNA expressed in leukocytes at time of stroke can stratify risk of HT in patients treated with edoxaban. Investigators will assess the rate of recurrent ischemic stroke, but recognize any differences between groups will be hypothesis generating only due to the small trial sample size.

Study Design:

LASER is a randomized controlled, parallel-group, two-arm, assessor-blinded trial with an associated registry. Patients with previously known or newly diagnosed AF-related ischemic stroke within five days will be randomized 2:1 to early (≤ 5 days) or delayed (6-14 days) edoxaban initiation. Ischemic stroke will be defined as evidence of acute focal cerebral infarction confirmed on CT/MRI and/or focal hypoperfusion/vessel occlusion on multimodal CT, or by sudden focal and objective neurological deficits (i.e NIHSS ≥ 1) of presumed ischemic origin persisting > 24 hours. A total of one hundred fifty patients from a comprehensive Canadian stroke center will be enrolled. Eligible patients will be randomized within five days of symptom onset after baseline imaging. Patients with spontaneous parenchymal hemorrhage (PH) (European Cooperative Acute Stroke Study (ECASS) grade PH1 or PH2 on the baseline imaging will not be eligible for randomization. These patients will be included in the registry portion of LASER and follow-up will be identical to that in the trial. The timing of edoxaban initiation in these patients will be at the discretion of the treating physician.

Eligible patients will be randomized 2:1 following open label simple randomization procedure to early (≤ 5 days) or delayed (6-14 days) edoxaban initiation via a centralized web-based randomization process, Research Electronic Data Capture (REDCap, Vanderbilt university). After randomization to early or delayed arms, the decision to time the edoxaban initiation within the specific arm will be at the treating physician's discretion. The rationale for the specific timing of treatment, within the randomization window, will also be recorded by surveying the treating physician in each case.