Abstract 65: Field Neuroprotective Therapy Followed by Intravenous Thrombolysis in a Phase 3 Clinical Trial

Abstract

Background: A highly promising treatment strategy for acute cerebral ischemia is 1) administration of neuroprotective therapy in the field to stabilize the penumbra, followed by 2) intravenous thrombolytic recanalization therapy to restore blood flow and rescue threatened tissue. The NIH Field Administration of Stroke Therapy-Magnesium (FAST-MAG) study is the first phase 3 RCT testing field initiation of neuroprotective therapy and enrollees are permitted to undergo FDA or national guideline approved recanalization therapies upon hospital arrival when clinically indicated. Objective: To characterize rates of utilization of intravenous (IV) thrombolysis with tissue plasminogen activator (TPA) in ischemic stroke patients enrolled in a prehospital study. Methods: In FAST-MAG, patients within 2 hours of last known well time transported by 353 ambulances to 59 hospitals are randomized to prehospital-initiated magnesium sulfate vs. placebo. Results: Among 1206 consecutive enrolled subjects, final diagnosis of the presenting event was acute cerebral ischemia in 861 (71.4%), intracranial hemorrhage (ICH) in 295 (24.5%), and stroke mimic in 48 (4%). IV TPA was used in 320 patients, 37% of those with a final diagnosis acute cerebral ischemia (ACI, stroke or TIA). Among the ACI patients, none had intracerebral hemorrhage (ICH) on initial imaging study. Among the ACI patients, compared with patients not treated with TPA, TPA-treated patients had worse stroke deficits both in the field (Los Angeles Motor Scale Score 4.2 v 3.35, p<0.0001) and on ED arrival (NIHSS 14 v 7, p<0.0001); and had shorter onset to paramedic evaluation (28 v 43 min, p=0.001) and onset to door (62 v 78 min, p=0.002); and more frequently had a history of HTN (83% v 77%, p = 0.034). TPA treated and non-treated patients were similar in age (71 v 71, p=0.960), sex (female in 47% v 44%, p=0.559), Hispanic ethnicity, race, prehospital and ED systolic and diastolic blood pressures, and other vascular risk factors. Conclusions: More than 1 in 3 acute ischemic stroke patients enrolled in the FAST-MAG trial are receiving IV TPA following their field initiation of study agent. When completed, FAST-MAG will have substantial power to evaluate whether there is a synergistic benefit of prehospital neuroprotection and early postarrival thrombolytic reperfusion therapy on clinical outcomes.