Introduction&Hypothesis: The aim of the present study was to investigate whether administration of edaravone, a free radical scavenger, before or during t-PA administration can increase the rate of early recanalization and improve the clinical outcome in stroke patients with major arterial occlusion.
Methods: YAMATO study is an investigator initiated, multicenter (17 hospitals in Japan), prospective, randomized, open labeled study. Acute stroke patients with horizontal (M1) or vertical (M2) portion of the middle cerebral artery occlusion within 4.5 h of onset were studied. The subjects were randomly allocated to the early edaravone (early-E) group (intravenous edaravone [30 mg] was started before or during t-PA administration) and the late edaravone (late-E) group (edaravone was started after t-PA administration). Primary outcome, defined as any early recanalization 1h after t-PA therapy. Secondary outcomes included the rate of the significant recanalization, defined as ≥50% of the territory of the occluded artery on magnetic resonance angiography, or the thrombolysis in cerebral infarction score ≥2b on digital subtraction angiography as well as the incidence of symptomatic intracerebral hemorrhage (sICH), and the favorable clinical outcome (modified Rankin scale [mRS] of 0-2) at 3 months after onset.
Results: One-hundred and sixty-six patients (96 men; median age [interquartile range], 78 [69-85] years) were randomized 1:1 to either the early-E group or the late-E group. Twenty-three (13.9%) had proximal M1 occlusion; 60 (36.1%), distal M1 occlusion; 83 (50%), M2 occlusion. Early recanalization was similarly observed in the early-E group and in the late-E group (53.1% vs. 53.0%, P=1.000). The rate of significant recanalization was also similar between the 2 groups (27.2% vs. 33.7%, p=0.399). sICH was occurred in 4 (4.8%) patients in the early-E group and in 2 (2.4%) in the late-E group (p=0.682). Among the 144 patients who were pre-morbid mRS of 0-2 and eligible for 3 months assessment, favorable outcome was seen in 53.9% in the early-E group and 57.4% in the late-E group (p=0.738)
Conclusions: The timing of the edaravone infusion should not affect the rate of early recanalization, sICH, or favorable outcome after t-PA therapy.