Prehospital neuroprotectant in combination with post-arrival thrombolytic therapy for acute ischemic stroke. Secondary analysis of the FAST-MAG prehospital trial.
Journal of stroke and cerebrovascular diseases · 2026-07-24 · Randomised trial
Abstract
OBJECTIVE: Prehospital neuroprotectant therapy in combination with thrombolysis is a potential treatment strategy in acute ischemic stroke allowing for earlier therapy start and bridging period until in-hospital therapies. We describe prehospital administration of magnesium sulfate (Mg) vs. placebo for neuroprotection followed by post-arrival thrombolysis (TPA). METHODS: We analyzed subjects who received TPA in the NIH Field Administration of Stroke Therapy Magnesium (FAST-MAG) clinical trial, a phase 3 randomized clinical trial of patients presenting within 2 h of last known well time (LKWT). Primary outcome was disability measured on the modified Rankin Scale (mRS) at 90 days. RESULTS: Among identified 401 cases, 214 received Mg and 187 received placebo followed by TPA. Mean (±SD) age was 70±13 years, 46% women, and median Los Angeles Motor Scale (LAMS) was 4 (IQR 3-5). Median LKWT to prehospital initiation time was 46 min (IQR 35-65), and 150 min (IQR 124-171) to thrombolysis. The median prehospital study infusion exposure prior to thrombolysis start was 93 (IQR 75-117) min. In patients with NIHSS >15, the Mg group had a higher proportion achieving favorable 90-day outcomes (mRS 0-2) and lower median LAMS scores compared with placebo, although these findings were not supported by overall 90-day outcomes mRS analysis and should be considered hypothesis-generating. CONCLUSIONS: Prehospital magnesium followed by alteplase was feasible and safe but did not demonstrate a significant overall clinical benefit. The main contribution of this analysis is to quantify the substantial pre-reperfusion exposure interval achievable with prehospital neuroprotective therapy, supporting this model for future agents requiring early biological exposure before reperfusion.