Epigallocatechin Gallate Extends Therapeutic Window of Recombinant Tissue Plasminogen Activator Treatment for Brain Ischemic Stroke: A Randomized Double-Blind and Placebo-Controlled Trial

Objectives: Recombinant tissue plasminogen activator (rt-PA) is a safe and effective treatment for acute brain ischemia stroke, albeit with a narrow therapeutic window. We aimed to assess the effect of epigallocatechin gallate (EGCG) in extending the rt-PA treatment window in this clinical trial among stroke patients. Methods: Patients were randomly assigned according to their onset-to-treatment time (OTT) and were then treated with rt-PA simultaneously with EGCG or placebo. Treatment outcome was assessed by the National Institutes of Health stroke scale (NIHSS) and plasma levels of matrix metalloproteinases (MMP)-2 and 9. Results: Administration of EGCG significantly improved treatment outcomes of patients in the delayed OTT strata, as evidenced by improved NIHSS scores. This improved treatment outcome was likely attributed to reduction in plasma levels of both MMP-2 and 9, as indicated by strong linear correlations between both MMPs and NIHSS scores in all patients. Conclusions: Epigallocatechin gallate could potentially be used as a supplement of traditional rt-PA treatment among stroke patients, particularly those with delayed OTT, to extend the otherwise narrow therapeutic window and improve the outcome in late stroke treatment.