Edaravone with and without .6 Mg/Kg Alteplase within 4.5 Hours after Ischemic Stroke: A Prospective Cohort Study (PROTECT4.5).

BACKGROUND: Edaravone is widely used to treat acute ischemic stroke (AIS) within 24 hours of onset. We aimed to evaluate current edaravone treatment practices and the efficacy and safety of edaravone used with recombinant tissue plasminogen activator (tPA) in AIS patients within 4.5 hours of onset. The results were compared with those of the Safe Implementation of Treatments in Stroke-International Stroke Thrombolysis Registry (SITS-ISTR) study.

METHODS: PROTECT4.5 was a prospective observational study conducted from April 2010 to March 2013 in Japan. The primary end points were favorable outcomes (modified Rankin Scale score [mRS] 0-1) at 3 months after onset and incidence of symptomatic intracranial hemorrhage (sICH) within 36 hours of treatment. For comparison with SITS-ISTR, patients were categorized based on the time from onset to treatment (within 3 hours of and 3-4.5 hours after onset) and baseline National Institutes of Health Stroke Scale score (NIHSS).

RESULTS: Among the 11,384 registered patients, 11,126 and 8274 patients were included in the safety and efficacy analysis populations, respectively. The proportions of patients with mRS 0-1 receiving edaravone alone and edaravone + tPA were 51.3% (95% confidence interval, 49.7%-52.8%) and 39.0% (37.6%-40.5%), respectively. The incidence of sICH within 36 hours after tPA treatment (edaravone + tPA group) was 1.6% (1.3%-2.0%). When compared with the SITS-ISTR results, those treated with edaravone + tPA appeared to show better outcomes in patients with NIHSS score ≥16.

CONCLUSIONS: The efficacy and safety of edaravone combined with tPA and administered within 4.5 hours of AIS onset were demonstrated with numerically lower incidence of sICH and better outcomes.