Efficacy and Safety of Mexidol® in Stroke Therapy (MIR)

Prospective International Multicenter Randomized, Double-blind, Placebo-controlled, Parallel-group Study of the Efficacy and Safety of Mexidol® in Sequential Treatment of Patients in the Acute and Early Recovery Periods of Ischemic Stroke

The main purpose of the clinical trial is to evaluate the efficacy and safety of Mexidol® in sequential treatment for patients in the acute and early recovery periods of ischemic stroke compared to placebo. The effect of adding Mexidol® to standard therapy on the degree of impairment of vital functions was assessed including the degree of disability (according to the Modified Rankin Scale, mRS), the severity of neurological symptoms (according to the National Institutes of Health Stroke Scale, NIHSS) and the level of mobility of patients (according to the Rivermead Mobility Index).

Study Overview

• Status: Completed
• Conditions: Ischemic Stroke
• Intervention / Treatment: Drug: Placebo; Drug: Mexidol (Ethylmethylhydroxypyridine Succinate)

Detailed Description

As the main purpose of the clinical study is to evaluate safety and efficacy of a neuroprotector (Mexidol®), it was crucial to develop strict protocol requirements that would help to avoid the challenges of estimation of neuroprotective effect for stroke therapy. The current treatment options for stroke are still limited and do not take into account rehabilitation period and patients' further quality of life.

As per protocol requirements, 313 participants were screened, 304 participants met all comprehensive eligibility criteria, 25 participants dropped out during the clinical trial period. The Modified Rankin Scale (mRS) was selected as the most representative primary outcome measuring tool due to the adequate representation of functional outcome. Additionally, the neuroprotective efficacy of Mexidol® was assessed for its ability to reduce stroke-related neurologic deficit, to improve mobility after stroke and to influence cognitive impairment and mood disorder symptoms.

• Study Type: Interventional
• Enrollment (Actual): 304
• Phase: Phase 3

Contacts and Locations

Study Locations

• Kazakhstan
  • Almaty, Kazakhstan, 050006
    • Almaty City Hospital № 7
• Russia
  • Kazan', Russia, 420103
    • Kazan City Hospital № 7
  • Kemerovo, Russia, 650014
    • Kemerovo City Clinical Hospital № 11
  • Krasnodar, Russia, 350086
    • Research Institute - Regional Clinical Hospital № 1
  • Moscow, Russia, 117997
    • Federal Center for Brain and Neurotechnology
  • Moscow, Russia, 117997
    • Russian National Research Medical University n.a. N. I. Pirogov
  • Rostov-on-Don, Russia, 344022
    • Rostov State Medical University
  • Saint Petersburg, Russia, 193312
    • Alexandrovskaya Hospital
  • Saint Petersburg, Russia, 196247
    • St. Petersburg Clinical Hospital № 26
  • Saint Petersburg, Russia, 197706
    • City Hospital № 40 of Kurortny District
  • Samara, Russia, 443095
    • Samara Regional Clinical Hospital n.a. V. D. Seredavin
  • Ulyanovsk, Russia, 432026
    • Central Clinical Medical and Sanitary Unit n.a. V. A. Egorov
  • Voronezh, Russia, 394066
    • Voronezh Regional Clinical Hospital № 1
  • Vsevolozhsk, Russia, 188643
    • Vsevolozhsk Clinical Interdistrict Hospital
  • Yaroslavl, Russia, 150030
    • Yaroslavl Clinical Hospital № 2 (ICU)
  • Yaroslavl, Russia, 150030
    • Yaroslavl Clinical Hospital № 2
• Uzbekistan
  • Tashkent, Uzbekistan, 100109
    • The first clinic of the Tashkent Medical Academy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Clinical diagnosis of first-ever hemispheric ischemic stroke (codes ICD-10: I63.0 - I63.9) with the time from onset of a stroke <48 hours.
• CT or MRI evidences of clinical diagnosis and no evidences of hemorrhagic stroke/hemorrhagic transformation of ischemic stroke.
• The written informed consent form (ICF) is signed and personally dated by the participant or by an impartial witness (by a person who is independent of the trial and cannot be unduly influenced by the people involved with the trial and who attends the informed consent process).
• The Modified Rankin Scale (mRS) score ≥3.
• The National Institutes of Health Stroke Scale (NIHSS) score from 9 to 15 points.
• Negative pregnancy test for women of childbearing age.
• Willingness to use reliable methods of contraception, and/or abstinence, for the duration of therapeutic product exposure.
• The ability to understand the purpose of research, risks associated with the research intervention, obligations and consequences of research participation and their right of withdrawing consent any time during the study.

Exclusion Criteria:

• BMI (Body Mass Index) > 35.
• Recurrent or hemorrhagic stroke confirmed by CT/MRI.
• Hemorrhagic transformation of ischemic stroke.
• Parkinson's disease/parkinsonism.
• Progressive Multiple Sclerosis.
• Intractable Epilepsy.
• Demyelinating diseases of central nervous system.
• Hereditary and degenerative diseases of the central nervous system.
• Infectious diseases of central nervous system in medical history.
• Traumatic brain injury with severe neurocognitive impairment in medical history.
• Congenital malformations of the nervous system or any neurological disorders that can affect participant's capability (including cognitive and motor skills) to follow protocol procedures.
• Thrombolysis or thrombectomy treatment prior the enrollment.
• Medical history of severe allergies.
• Evidence of hypersensitivity reactions or intolerance associated with ethylmethylhydroxypyridine.
• Evidence of lactose intolerance, galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption.
• Acute surgical pathology.
• Evidence of clinically significant first identified disorder or disease that can affect participant's ability to participate in the clinical trial.
• Evidence of clinically significant severe disease/condition that can affect participant's ability to participate in the clinical trial: respiratory diseases, cardiovascular diseases (CVDs) including SAP ≥ 200 mm Hg and DAP ≥ 100 mm Hg, liver disease with elevation of ALT/AST > 2 × ULN, kidney disease (еGFR<30ml/min/1.73 m2), endocrine disorders and diseases, gastrointestinal diseases, pulmonary embolism (PE), deep vein thrombosis (DVT), floating thrombus, convulsive syndrome, uncontrolled hyperthermia, uncontrolled hyperglycemia.
• Medical history of severe mental disorder.
• Dementia of the Alzheimer type (DAT).
• Medical history of cancers within 5 years prior to enrollment.
• Medical history of alcohol/drug addiction.
• Pregnancy or breastfeeding.
• Prescription or use of prohibited medications within 2 weeks prior to enrollment.
• Positive HIV, syphilis, hepatitis B and C test.
• Positive COVID-19 test.
• Participation in another trial within 3 months prior to enrollment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mexidol®; Participants received Mexidol® IV 500 mg 2 times a day for 10 days, then Mexidol® FORTE 250 orally 250 mg 1 tablet 3 times a day for 60 days	Drug: Mexidol (Ethylmethylhydroxypyridine Succinate); 50 mg/ml IV solution, 250 mg tablets
Placebo Comparator: Placebo; Participants received Placebo matching Mexidol® IV 500 mg 2 times a day for 10 days, then Mexidol® FORTE 250 orally 250 mg 1 tablet 3 times a day for 60 days	Drug: Placebo; Placebo IV solution, Placebo tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in the Modified Rankin Scale (mRS) Scores at the End of the Course of Therapy	The Modified Rankin Scale (mRS) is used to measure the degree of disability in patients who have had a stroke. Possible scores range from 0 (no symptoms at all) to 5 (dead) [6 point scale: min value 0, max value 5, higher scores mean a worse outcome]. Change = (Visit 4, Day 71(+2) - Visit 0, Day 0-1 Scores).	Baseline, Day 71

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects Having Modified Rankin Scale (mRS) Scores >3 (Higher Degree of Disability) at the End of the Course of Therapy	The Modified Rankin Scale (mRS) is used to measure the degree of disability in patients who have had a stroke. Possible scores range from 0 (no symptoms at all) to 5 (dead) [6 point scale: min value 0, max value 5, higher scores mean a worse outcome].	Day 71
Percentage of Subjects Having Modified Rankin Scale (mRS) Scores 0-1 (Normal or Lower Degree of Disability) at the End of the Course of Therapy	The Modified Rankin Scale (mRS) is used to measure the degree of disability in patients who have had a stroke. Possible scores range from 0 (no symptoms at all) to 5 (dead) [6 point scale: min value 0, max value 5, higher scores mean a worse outcome].	Day 71
Change From Baseline in the National Institutes of Health Stroke Scale (NIHSS) Score at the End of the Course of Therapy	The National Institutes of Health Stroke Scale (NIHSS) is a systematic assessment tool that provides a quantitative measure of stroke-related neurologic deficit. The NIHSS is a 15-item neurologic examination stroke scale used to evaluate the effect of acute cerebral infarction on the levels of consciousness, language, neglect, visual-field loss, extraocular movement, motor strength, ataxia, dysarthria, and sensory loss. Ratings for each item are scored with 3 to 5 grades with 0 as normal, and there is an allowance for untestable items. The individual scores from each item are summed in order to calculate a patient's total NIHSS score. The maximum possible score is 42 (severe stroke), with the minimum score being a 0 (no stroke symptoms) [43 point scale: min value 0, max value 42, higher scores mean a worse outcome]. Change = (Visit 4, Day 71(+2) - Visit 0, Day 0-1 Scores).	Baseline, Day 71
Change From Baseline in the Rivermead Mobility Index (RMI) Score at the End of the Course of Therapy	The Rivermead Mobility Index (RMI) is a hierarchical mobility scale used in neurological rehabilitation. It includes 15 items related to bed mobility, transfers, walking, stair use, and running. The test is comprised of 14 questions, and the patient is then asked to stand for 10 seconds without any aid. Each response is scored yes or no with 1 point for each yes answer. The scores are summed with a range from 0 (poor mobility) to 15 (excellent mobility) [16 point scale: min value 0, max value 15, higher scores mean a better outcome]. Change = (Visit 4, Day 71(+2) - Visit 1, Day 1 Scores).	Baseline, Day 71
Change From Baseline in the Montreal Cognitive Assessment (MoCA) Score at the End of the Course of Therapy	The Montreal Cognitive Assessment (MoCA) is a 30-point validated scale that covers multiple cognitive domains including spatiotemporal orientation, sustained attention, visuospatial function, executive function, verbal memory, language, naming, and abstract thinking [31 point scale: min value 0, max value 30, higher scores mean a better outcome]. Change = (Visit 4, Day 71(+2) - Visit 1, Day 1 Scores).	Baseline, Day 71
Change From Baseline in the Hospital Anxiety and Depression Scale Score, Domain ANXIETY (HADS-A), at the End of the Course of Therapy	The Hospital Anxiety and Depression Scale (HADS) is a brief self-report measure that was specifically designed to screen for distinct dimensions of anxiety and depression in nonpsychiatric hospital departments; somatic symptoms were excluded [22 point scale for each domain (Anxiety or Depression): min value 0, max value 21, higher scores mean a worse outcome]. Change = (Visit 4, Day 71(+2) - Visit 1, Day 1 Scores).	Baseline, Day 71
Change From Baseline in the Hospital Anxiety and Depression Scale Score, Domain DEPRESSION (HADS-D), at the End of the Course of Therapy	The Hospital Anxiety and Depression Scale (HADS) is a brief self-report measure that was specifically designed to screen for distinct dimensions of anxiety and depression in nonpsychiatric hospital departments; somatic symptoms were excluded [22 point scale for each domain (Anxiety or Depression): min value 0, max value 21, higher scores mean a worse outcome]. Change = (Visit 4, Day 71(+2) - Visit 1, Day 1 Scores).	Baseline, Day 71

Collaborators and Investigators

• Sponsor: Pharmasoft

Publications and helpful links

General Publications

• Shamalov NA, Fedin AI, Rakhimbaeva GS, Nurguzhaev ES, Khasanova DR, Solovyova EY, Melnikova EV, Yanishevsky SN, Mashin VV, Pizova NV, Poverennova IE, Chuprina SE, Agafina AS, Roshkovskaya LV. [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)]. Zh Nevrol Psikhiatr Im S S Korsakova. 2025;125(8. Vyp. 2):40-53. doi: 10.17116/jnevro202512508240. Russian.
• Koltsov IA, Shchukin IA, Fidler MS, Glukhareva AP, Chubykin VI. [Multimodal antioxidant therapy in ischemic stroke: from MIR trial to bedside]. Zh Nevrol Psikhiatr Im S S Korsakova. 2025;125(12. Vyp. 2):64-71. doi: 10.17116/jnevro202512512264. Russian.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): November 18, 2019
• Primary Completion (Actual): August 18, 2023
• Study Completion (Actual): August 18, 2023

Study Registration Dates

• First Submitted: May 24, 2024
• First Submitted That Met QC Criteria: May 30, 2024
• First Posted (Actual): May 31, 2024

Study Record Updates

• Last Update Posted (Actual): December 30, 2025
• Last Update Submitted That Met QC Criteria: December 8, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Antioxidants; Stroke; Ischemic Stroke; Neuroprotection; Acute Stroke; Stroke Rehabilitation; Cerebral Stroke; Brain Ischemia; Neuroprotective Agents; Recovery of Function; Acute Cerebrovascular Accident; Mexidol; Ethylmethylhydroxypyridine Succinate
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Ischemic Stroke; Stroke; Brain Ischemia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Protective Agents; Psychotropic Drugs; Antioxidants; emoxypine succinate; ethylmethylhydroxypyridine succinate
• Other Study ID Numbers: MexidolMIR2023; PHS-APIS-004-MEX-SOL-TAB (Other Identifier: Ministry of Health, Russian Federation)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No