Abstract Body: Background: There are few recovery options available for stroke survivors. This randomized trial aims to confirm the findings of the EMAGINE 1.0 trial suggesting that an app-controlled, non-invasive, extremely low-frequency and low-intensity electromagnetic network targeting field (ENTF) stimulation therapy initiated in the subacute phase following ischemic stroke is effective in achieving freedom from disability. Objectives: Evaluate the effectiveness and safety of ENTF stimulation therapy, when initiated in the subacute phase after ischemic stroke, in attaining freedom from disability at three months. Design: Prospective, multicenter, double-blind, randomized, sham-controlled, parallel two-arm and three-stage study, following a sample-size–adaptive design with a single planned interim assessment. PopulationStudied: Patients within 4-21 days post ischemic stroke, age 22-80, with mRS score of 3-4, FMA-UE score between 10-45. The initial planned sample size is 122 participants, which may increase up to 305 based on interim assessment. Intervention: Stage I (day 4-90 post-stroke, randomized) ENTF treatments (active or sham) for 60 minutes 5 times per week in conjunction with rehabilitative exercises, in acute hospital, inpatient rehabilitation, and home settings. In Stage II (day 90-180 post-stroke) all eligible participants in both arms will receive active ENTF treatment and concurrent exercises 5 times per week Outcome Measures: The primary efficacy outcome will be the proportion of patients achieving an excellent outcome defined as a Modified Rankin Scale (mRS) score of 0-1 at the 90-day post-stroke assessment. Secondary outcomes include: additional analyses of the mRS, SIS-Hand, SIS-16, 10 MWT (gait speed), EQ-5D, FMA-UE, 9-HPT, with focal point on day-90, and mRS outcomes at day180 post stroke. Safety will also be monitored, in addition to several tertiary/exploratory outcomes.
Analysis: A 1-sided hypothesis with a type 1 error rate of 2.5% will compare the proportion of patients who achieve an mRS of 0-1 at 90 days between the 2 randomized treatment groups (active and sham). An interim assessment is planned for re-estimation of the target sample size. The primary endpoint based on proportions will be compared between the treatment groups using a logistic regression model; The primary analysis of the primary effectiveness endpoint will use multiple imputation. Trial Status:Enrollment initiated August, 2024.