Abstract A081: Low-Frequency REpetitive TRanscranial Magnetic Stimulation Combined with Endovascular Treatment in ACute Ischaemic StrokE (RETRACE II): a randomised double-blind controlled multicentre phase II pilot study

Background: Despite high recanalization rates with endovascular therapy, fewer than half of patients achieve functional independence, underscoring the need for adjunctive neuroprotective therapies. We aim to evaluate whether adjunctive Low-frequency repetitive transcranial magnetic stimulation (LF-rTMS), initiated in the hyperacute phase after EVT, improves neurological outcomes. Methods: RETRACE II is a multicenter, randomized, double-blind, sham-controlled trial. Acute ischemic stroke patients who received EVT were randomly assigned (1:1) to either active LF-rTMS or sham stimulation. The LF-rTMS group received 1200 pulses of 1 Hz rTMS targeting the ipsilesional primary motor cortex, delivered twice daily for three consecutive days, starting within 24 hours of stroke onset. The primary outcome was early neurological improvement at 3 days post-treatment, defined as a ≥4-point decrease in NIHSS or NIHSS score of 0–1 from baseline. Key secondary outcomes included infarct volume on MRI at 7 days and the proportion of patients achieving an excellent recovery (modified Rankin Scale [mRS] 0–1) at 90 days. Safety endpoints included symptomatic intracranial haemorrhage (sICH), neurological deterioration (NIHSS increase ≥4). Findings: Sixty patients (mean age 64 years, 72% male) were enrolled. At 3 days post-stroke, the proportion of patients reaching the early neurological improvement was 70% in both groups, with no statistically significant difference observed after adjusting for age, NIHSS, and time from intervention to symptom onset (OR 1.39, 95%CI 0.38-5.05, p = 0.62). Final infarct volume at day 7 was numerically lower with LF-rTMS than with sham stimulation (15.36 mL [4.44–33.61] vs 21.25 mL [6.29–48.59], p=0.82). At 90 days, the LF-rTMS group showed a higher rate of excellent recovery than the sham group (66.7% vs 53.3%), but this difference was not statistically significant in the pilot sample (OR 2.62, 95% CI 0.76–9.12; p=0.12). (Figure) In patients treated within 15-24 hours, the LF-rTMS group shows a significantly higher proportion of excellent recovery (100%) than the sham group (47.4%). (χ 2 =9.31, p=0.002) All safety outcomes were comparable between groups. Interpretation: In this phase II pilot trial, adjunctive LF-rTMS initiated within 24 hours of stroke onset was feasible and safe in patients undergoing EVT, and it showed potential efficacy in improving long-term functional outcomes. (ClinicalTrials.gov number, NCT06064747.)