Design for the everest randomized trial of cortical stimulation and rehabilitation for arm function following stroke

Background. Cortical stimulation (CS) combined with rehabilitation may improve upper limb motor function after stroke. Objective. Describe the study design for the Everest Clinical Trial, a randomized single-blinded pivotal device trial, testing safety and efficacy of epidural CS delivered during rehabilitation for upper limb motor function in patients with ischemic stroke. Method. A total of 174 participants from 21 centers with hemiplegia at least 4 months after acute ischemic stroke are randomized in a 2:1 ratio to investigational or control groups. Investigational patients undergo implantation of cortical electrode and pulse generator and receive 6 weeks of upper limb rehabilitation with subthreshold CS delivered only during therapy. Control group patients receive the same therapy without device implantation or stimulation. Primary outcome measures include the upper extremity Fugl-Meyer (UEFM) score and the arm motor ability test (AMAT) measured at baseline and 1, 4, 12, and 24 weeks following rehabilitation treatment with primary endpoint at 4 weeks following treatment. A successful outcome is defined as an improvement in UEFM of at least 4.5 points and in AMAT of at least 0.21 points from baseline to primary endpoint. A 20% better success rate between investigational and control groups will be considered clinically meaningful. Adverse events occurring during the study will be identified. Results. Not applicable. Conclusions. The Everest Clinical Trial is the first randomized pivotal trial on the safety and efficacy of direct CS delivered during rehabilitation for recovery of upper limb motor function in patients with ischemic stroke.