Results of the international multicenter randomized, double-blind, placebo-controlled clinical trial for the evaluation of the efficacy and safety of the sequential therapy with ethylmethylhydroxypyridine succinate in patients in the acute and early recovery periods of ischemic stroke (MIR)

Objective. Evaluation of the comparative efficacy and safety of ethylmethylhydroxypyridine succinate therapy with Mexidol, solution for intravenous and intramuscular administration, 50 mg/ml, and Mexidol FORTE 250, film-coated tablets, 250 mg, during their sequential use in patients in the acute and early recovery periods of ischemic stroke (IS) compared to placebo. Material and methods. The clinical trial was conducted as a prospective international multicenter randomized double-blind placebo-controlled parallel-group trial. Data from the randomized patients in the acute and early recovery periods of ischemic stroke were collected at 4 visits. Patients were divided into two equal groups: the main group (standard therapy+Mexidol at a dose of 500 mg twice a day administered intravenously in 100—200 ml of 0.9% NaCl solution for 10 days, followed by Mexidol FORTE at a dose of 250 mg three times a day for 60 days) and the placebo group (standard therapy+placebo administered following the same scheme as the main group). The primary efficacy endpoint was the amount of change in patient status assessed with the Modified Rankin Scale (mRS) at the end of the therapy compared to the baseline level (measured in scores). Results. A total of 304 patients in the acute and early recovery periods of IS were randomized into the trial. The trial groups were matched for sex, age and anthropometric characteristics. The statistically significant differences confirming the efficacy of therapy with Mexidol were obtained. The Mexidol group showed a significant reduction in the degree of disability, according to the Modified Rankin Scale (mRS), a neurological improvement, according to the National Institutes of Health Stroke Scale (NIHSS), an increase in mobility, according to the Rivermead Mobility Index, and a strong tendency to the reduction of cognitive deficit, according to the Montreal Cognitive Assessment (MoCA). Statistically significant differences in favor of Mexidol compared to placebo were observed for the difference in median mRS scores at Visit 4 against the baseline level (p=0.003), the difference in median NIHSS scores (p<0.001) and in median Rivermead Mobility Index scores (p=0.014). Treatment with Mexidol was also associated with a reduction in the number of disabled patients (p=0.016) and an increase of patients with scores of 0—1 on the mRS at Visit 4 (p=0.002) when compared to placebo. Adverse events (AEs) were reported in 35 patients (23%) in the Mexidol group (42 AEs in total) and in 35 patients (23%) in the placebo group (43 AEs in total) (p=1.000). Conclusion. According to the clinical trial results, statistically significant differences were obtained, which confirm the greater efficacy of therapy using Mexidol compared to placebo in patients in the acute and early recovery periods of IS of moderate severity. This was observed in terms of reducing the degree of patients’ disability and the severity of neurological symptoms, in terms of improving motor capabilities and increasing mobility. A similar safety profile was demonstrated for the long-term sequential therapy with Mexidol and Mexidol FORTE 250 and placebo.