Multimodal antioxidant therapy in ischemic stroke: from MIR trial to bedside

OBJECTIVE: To discusses the practical healthcare implications of the MIR trial and its post-hoc analyses. MATERIAL AND METHODS: MIR was an international multicenter randomized double-blind placebo-controlled trial conducted in 17 centers In Russia, Kazakhstan, and Uzbekistan. 304 patients were randomized, and 279 patients were included in the per-protocol analysis (276 for clinical scales applicable to survivors only). Non-reperfused patients aged 40-75 years with first-ever hemispheric IS, presenting ≤48 hours from onset with CT/MRI signs of ischemia or no signs of intracerebral hemorrhage, were included. Additionally, at screening, the included patients had a National Institutes of Health Stroke Scale (NIHSS) score of 9-15 and a modified Rankin Scale score (mRS) of 3 or higher. In the treatment group, patients received sequential therapy as follows: 500 mg (10 mL) of intravenous Mexidol diluted in 100-200 ml of normal saline twice per day for 10 days, followed by 250 mg of Mexidol FORTE 250 orally thrice per day for 60 days. In the control group, patients received a placebo administered in a similar manner. The primary endpoint was a change in mRS score from baseline at days 69-73. The trial protocol was registered in the Registry of Permits for Conducting Clinical Trials (PHS-APIS-004-MEX-SOL-TAB) and the ClinicalTrials.gov registry (NCT06437626). In addition, several post-hoc analyses showed that sequential multimodal antioxidant treatment was associated with a 2.2-fold increase in favorable functional outcome odds (mRS score of 0-1) and a 3.9-fold increase in complete neurological recovery odds (NIHSS score of 0) at day 69-73 compared to placebo. DISCUSSION: The MIR randomized clinical trial showed that 70-day sequential therapy with Mexidol and Mexidol FORTE 250 was superior to placebo in non-reperfused patients with first-ever IS and a baseline NIHSS score of 9-15.