ENTF-Stroke-IPD
ENTF Neuromodulation Yields Reduced Disability After Stroke: An Individual Participant-Level Data Meta-Analysis
Clinical Question
Does electromagnetic network-targeted field (ENTF) neuromodulation reduce disability compared with sham stimulation in patients with subacute ischemic stroke and moderate-severe entry disability?
Study Overview
Objective
To perform a pooled individual patient-level data meta-analysis of two randomized sham-controlled trials to characterize with greater statistical power the effect of electromagnetic network-targeted field (ENTF) brain stimulation therapy on disability and recovery after subacute ischemic stroke.
Study Summary
- Freedom-from-disability (mRS 0-1) at 8-12 weeks was higher with active ENTF than sham (33.8% vs 11.9%; P=0.005)
- Ordinal shift across 3 disability strata (mRS 0-1, 2, >2) also favored ENTF (P=0.009)
- Focused upper extremity motor endpoints nonsignificantly favored ENTF
- No device- or procedure-related serious adverse events were observed
- ENTF supported as a promising therapy for stroke recovery in patients with moderate-severe entry disability
Intervention
Electromagnetic network-targeted field (ENTF) brain stimulation therapy versus sham stimulation, administered in the subacute period after ischemic stroke.
Patients per Arm
Active ENTF n=65; Sham n=59
Bottom Line
In pooled IPD from two randomized sham-controlled trials, active ENTF neuromodulation increased freedom-from-disability (mRS 0-1) at 8-12 weeks compared with sham (33.8% vs 11.9%; P=0.005), improved the overall ordinal disability distribution, and demonstrated an attractive safety profile with no device- or procedure-related serious adverse events, supporting ENTF as a promising therapy for stroke recovery.
Major Points
- Pooled individual patient-level data meta-analysis of 2 double-blind, randomized, sham-controlled trials (BQ3 [NCT04039178] and EMAGINE 1 [NCT05044507]) totaling 124 patients.
- Active ENTF more than doubled the rate of freedom-from-disability (mRS 0-1) at 8-12 weeks (33.8% vs 11.9%; P=0.005).
- Ordinal shift analysis across mRS strata (0-1, 2, >2) also favored ENTF (P=0.009).
- Focused upper extremity motor endpoints nonsignificantly favored ENTF.
- No device- or procedure-related serious adverse events were observed.
- Population was subacute (therapy started 14.5 days poststroke on average) and moderate-severely disabled at entry (99.2% had mRS 3-4).
Design
Study Type: Pooled individual participant-level data (IPD) meta-analysis of two randomized, double-blind, sham-controlled trials
Randomization: 1
Blinding: Double-blind (pooled from two double-blind trials)
Allocation: not reported
Enrollment Period: not reported
Follow-up Duration: 8 to 12 weeks
Countries:
Sample Size: 124
Analyzed: 124
Analysis: Pooled IPD analysis; primary analysis of freedom-from-disability (mRS 0-1); ordinal mRS shift analysis across 3 disability strata (0-1, 2, >2); focused upper extremity motor endpoint analyses
Power Calculation: not reported
Registration: BQ3 NCT04039178; EMAGINE 1 NCT05044507
Inclusion Criteria
- Ischemic stroke 4 to 21 days prior
- Fugl-Meyer assessment-upper extremity score of 10 to 45
- For EMAGINE 1 participants: study entry modified Rankin Scale score of 3 to 4
Arms
| Field | Active ENTF | Control |
|---|---|---|
| N | 65 | 59 |
| Intervention | Electromagnetic network-targeted field (ENTF) brain stimulation therapy | Sham stimulation |
| Duration | not reported | not reported |
Outcomes
| Outcome | Type | Control | Intervention | HR / OR / RR | P-value |
|---|---|---|---|---|---|
| Freedom-from-disability, defined as modified Rankin Scale score 0-1 | Primary | 11.9% (sham) | 33.8% (active ENTF) | 33.8% (active ENTF) vs 11.9% (sham), favoring ENTF | 0.005 |
| Ordinal mRS shift across 3 disability strata (mRS 0-1, 2, and >2) at 8-12 weeks | Secondary | 0.009 | |||
| Disability change (delta mRS) from study entry to 8-12 weeks | Secondary | not reported | |||
| Focused upper extremity motor endpoints (2 endpoints) | Secondary | not reported | |||
| Device- or procedure-related serious adverse events | Safety | None reported | |||
| Serious Adverse Events (device- or procedure-related) | Adverse | None | |||
Subgroup Analysis
not reported
Criticisms
- Small pooled sample size (n=124) despite IPD approach.
- Population is heavily selected for moderate-severe entry disability (99.2% mRS 3-4), limiting generalizability to milder strokes.
- Focused upper extremity motor endpoints did not reach statistical significance, tempering the mechanistic link between the stimulation and motor recovery.
- The pooled analysis was funded by the device manufacturer (Brain.Q Technologies), with multiple author financial ties to the sponsor.
- Follow-up limited to 8-12 weeks; durability of benefit unknown.
Funding
Brain.Q Technologies Ltd
Based on: ENTF-Stroke-IPD (Stroke, 2026)
Authors: Saver JL, Stein J, Cramer SC, ..., Bornstein NM
Citation: Stroke. 2026;57(9):2813-2821. doi:10.1161/STROKEAHA.125.054959
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