Abstract A071: Pooled analysis of two randomized trials of ENTF therapy after ischemic stroke

As ischemic stroke mortality has fallen with reperfusion therapy advance, post-stroke disability has increased commensurately. Additional recovery interventions are needed. Extremely low-frequency (1–100 Hz), low-intensity (≤1 Gauss) electromagnetic field brain stimulation—electromagnetic network-targeted field (ENTF) therapy—is a promising approach. Preclinical studies show that oscillatory fields mimicking healthy CNS rhythms induce neuroprotective mechanisms and support functional network reorganization. Two pilot randomized, sham-controlled trials have shown safety and signals of efficacy. We undertook a pooled analysis to characterize with greater statistical power the effect of ENTF in promoting recovery and reducing disability in patients with post-stroke moderate-severe disability and upper extremity motor impairment. We pooled individual patient-level data from two double-blind, randomized, sham-controlled studies—BQ3 (NCT04039178) and EMAGINE-1 (NCT05044507)—enrolling participants 4–21 days post-ischemic stroke with baseline modified Rankin Scale (mRS) 3–4 and Fugl-Meyer Assessment Upper-Extremity (FMA-UE) 10–45. The primary outcome was freedom from disability (mRS 0–1) at 90d. Secondary outcomes were 90d mRS distribution, mRS change from entry to 90d, and motor/cognitive endpoints (FMA-UE, MoCA). Between-trial variance was addressed with mixed-effects modeling with random effects. Altogether, 124 patients were included (active n=65, sham n=59). Mean age 58.2 + 13.1 years; 31% female; baseline mRS 3.9±0.36; FMA-UE 25.3±10.6; therapy started median day 14 (IQR 8) post-stroke. Baseline features were well-balanced across treatment groups. At 90d, freedom from disability was higher with active than sham (33.8% vs 11.9%; p=0.005). Ordinal shift across three disability strata (mRS 0–1, 2, >2) favored active (p=0.009). Single-domain motor and cognitive endpoints numerically favored active but were not significant. Treatment-group mRS distributions at baseline and 90d are shown in the Figure; full outcomes appear in Table 1. Safety analyses showed no device- or procedure-related serious adverse events. Across two randomized, sham-controlled trials, ENTF showed efficacy in reducing global disability among subacute ischemic stroke patients with moderate–severe baseline disability. These findings, together with an attractive safety profile, support ENTF as a promising therapy for stroke recovery.