Randomised evaluation of low-dose rtPA and intensive BP lowering in acute ischemic stroke: the enchanted trial

Abstract

Background: Embolic stroke of undetermined source (ESUS) is a nonlacunar stroke without significant proximal arterial stenosis or an identified high-risk source of cardioembolism. The risk of recurrent stroke in ESUS patients remains substantial. Anticoagulation with a factor Xa inhibitor could optimize management in this patient population. Objective: NAVIGATE ESUS aims to determine whether rivaroxaban is superior to aspirin for reducing the risk of recurrent stroke and systemic embolism after recent ESUS. Patients and Methods: NAVIGATE ESUS is a multicenter, international, double-blind, active-controlled randomized clinical trial. Participants with ESUS aged ≥18 years will be randomized to either rivaroxaban 15 mg daily or aspirin 100 mg daily (1:1 blinded randomization) within 6 months of their qualifying stroke. Patients with CT or MRI-confirmed non-lacunar ischemic strokes will be eligible in the absence of relevant extracranial arterial occlusion/ stenosis ≥50%, history/evidence of atrial fibrillation after at least 24 hours of cardiac monitoring, intracardiac thrombus on echocardiography, or other identified stroke etiology. Patients with established indications for chronic anticoagulation or antiplatelet therapy, and/or GFR b 30 mL/min/1.73/m 2 will not be eligible. The primary outcome is time to recurrent stroke or systemic embolism.Recruitment of 7000 participants began in December of 2014 and will continue at 450 sites in 31 countries, including 54 Latin American sites. With 450 primary events anticipated, the study will have 90% power to detect a 30% reduction in the primary outcome by rivaroxaban vs. aspirin. Conclusion: NAVIGATE ESUS will provide randomized controlled data on optimal antithrombotic therapy for secondary stroke prevention in patients with ESUS.