New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial versus ASA to Prevent Embolism in Embolic Stroke of Undetermined Source (NAVIGATE ESUS)
To evaluate whether rivaroxaban is superior to aspirin in reducing the risk of recurrent stroke and systemic embolic events in patients with a recent ESUS. Patients who fulfill all inclusion and none of the exclusion criteria after giving informed consent will be randomly allocated 1:1 to either rivaroxaban 15mg or aspirin 100mg orally once daily. Randomization will be stratified by country and age <60 and ≥60 years. No more than 10% of the total patient population will be randomized into the age group <60 years. The study is event-driven and thus, all patients will be treated (or followed-up in case of premature discontinuation of study medication) until the required approximately 450 confirmed primary efficacy outcomes are expected to have occurred.
Multicenter, randomized, double-blind, double-dummy, active-comparator, event-driven, superiority phase III study
The primary efficacy objective is:
• To evaluate whether rivaroxaban is superior to aspirin in reducing the risk of recurrent stroke and systemic embolism in patients with a recent ESUS
The secondary efficacy objective is:
• To evaluate whether rivaroxaban is superior to aspirin in reducing cerebrovascular events, cardiovascular events, and mortality in patients with a recent ESUS
The safety objective is to document the incidence of clinically relevant bleeding
Robert Hart, Stuart Connolly
Robert G. Hart, M.D., Mukul Sharma, M.D., Hardi Mundl, M.D., Scott E. Kasner, M.D., Shrikant I. Bangdiwala, Ph.D., Scott D. Berkowitz, M.D., Balakumar Swaminathan, M.Sc., Pablo Lavados, M.D., Yongjun Wang, M.D., Yilong Wang, M.D., Antonio Davalos, M.D., Nikolay Shamalov, M.D., et al., for the NAVIGATE ESUS Investigators. Rivaroxaban for Stroke Prevention after Embolic Stroke of Undetermined Source. NEJM, June 2018, DOI: 10.1056/NEJMoa1802686.