Bayer NAVIGATE ESUS study stopped early due to little chance to achieve overall benefit

Bayer AG and development partner Janssen Research & Development, LLC have announced that the Phase III NAVIGATE ESUS study evaluating the efficacy and safety of rivaroxaban (Xarelto®) for the secondary prevention of stroke and systemic embolism in patients with a recent embolic stroke of undetermined source (ESUS) has been halted. According to the suggestion by the Independent Data Monitoring Committee (IDMC) after a planned interim analysis, the trial was stopped early as it showed comparable efficacy between the rivaroxaban and aspirin arms and very small chance to achieve overall benefit if the study were finished. While bleeding rates were low generally, an increase in bleeding was observed in the rivaroxaban arm compared to the low dose aspirin arm. The decision was taken jointly by the Academic Leadership of the trial and the sponsor Bayer.

The decision to halt the experiment was taken jointly by the Academic Leadership of the trial and the sponsor Bayer.

ESUS refers to patients with embolic stroke documented by neuroimaging for which the cause remains unidentified despite thorough investigations attempting to rule out established cardiac and vascular sources. It does not include patients with atrial fibrillation or established atherosclerotic disease and therefore the patient population in NAVIGATE ESUS differs from the currently approved indications for rivaroxaban. Despite recommended treatments, the stroke recurrence risk for patients with ESUS remains substantial.

"Patients with ESUS currently have limited treatment options and the role of anticoagulants in this area remains uncertain. We will now analyze the data from NAVIGATE ESUS to better understand this outcome and its implications," said Dr Joerg Moeller, Member of the Executive Committee of Bayer AG’s Pharmaceutical Division and Head of Development. "Patients will be contacted by their physician to switch to the standard of care, aspirin. Patients should not stop trial medication without consultation of their physicians. We are committed to continuing the extensive investigation of rivaroxaban for patients at risk of deadly blood clots."

The Phase III NAVIGATE ESUS study has enrolled 7,214 patients from 459 sites across 31 countries worldwide. In the study, patients were randomized to receive either rivaroxaban 15 mg once daily or aspirin 100 mg once daily alone. The primary efficacy endpoint was a composite of stroke (ischemic, hemorrhagic and undefined stroke, transient ischemic attack with positive neuroimaging) and systemic embolism. The primary safety endpoint was major bleeding according to the criteria of the International Society on Thrombosis and Haemostasis (ISTH).

A complete data analysis is expected to be presented at an upcoming medical meeting in 2018.