Efficacy and Safety of Mexidol® in Stroke Therapy

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

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT06437626

Acronym

MIR

Enrollment

304

Registered

2024-05-31

Start date

2019-11-18

Completion date

2023-08-18

Last updated

2025-12-30

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Ischemic Stroke

Keywords

Stroke, Ischemic Stroke, Neuroprotective Agents, Antioxidants, Stroke Rehabilitation, Recovery of Function, Brain Ischemia, Acute Stroke, Acute Cerebrovascular Accident, Cerebral Stroke, Neuroprotection, Mexidol, Ethylmethylhydroxypyridine Succinate

Brief summary

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).

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.

Interventions

DRUGMexidol (Ethylmethylhydroxypyridine Succinate)

50 mg/ml IV solution, 250 mg tablets

DRUGPlacebo

Placebo IV solution, Placebo tablets

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

40 Years to 75 Years

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
Change From Baseline in the Modified Rankin Scale (mRS) Scores at the End of the Course of Therapy	Baseline, Day 71	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).

Secondary

Measure	Time frame	Description
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	Day 71	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 From Baseline in the National Institutes of Health Stroke Scale (NIHSS) Score at the End of the Course of Therapy	Baseline, Day 71	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).
Change From Baseline in the Rivermead Mobility Index (RMI) Score at the End of the Course of Therapy	Baseline, Day 71	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).
Percentage of Subjects Having Modified Rankin Scale (mRS) Scores >3 (Higher Degree of Disability) at the End of the Course of Therapy	Day 71	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 From Baseline in the Hospital Anxiety and Depression Scale Score, Domain ANXIETY (HADS-A), at the End of the Course of Therapy	Baseline, Day 71	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).
Change From Baseline in the Hospital Anxiety and Depression Scale Score, Domain DEPRESSION (HADS-D), at the End of the Course of Therapy	Baseline, Day 71	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).
Change From Baseline in the Montreal Cognitive Assessment (MoCA) Score at the End of the Course of Therapy	Baseline, Day 71	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).

Countries

Kazakhstan, Russia, Uzbekistan

Participant flow

Participants by arm

Arm	Count
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 Mexidol: 50 mg/ml IV solution, 250 mg tablets	152
Placebo Participants received Mexidol 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 Placebo: Placebo IV solution, Placebo tablets	152
Total	304

Baseline characteristics

Characteristic	Mexidol®	Total	Placebo
Age, Continuous	62.45 years STANDARD_DEVIATION 7.88	62.53 years STANDARD_DEVIATION 7.68	62.61 years STANDARD_DEVIATION 7.49
Hospital Anxiety and Depression Scale, domain ANXIETY (HADS-A)	6 units on a scale	5 units on a scale	5 units on a scale
Hospital Anxiety and Depression Scale, domain DEPRESSION (HADS-D)	6 units on a scale	5 units on a scale	5 units on a scale
Modified Rankin Scale (mRS)	3.90 units on a scale STANDARD_DEVIATION 0.5	3.92 units on a scale STANDARD_DEVIATION 0.49	3.94 units on a scale STANDARD_DEVIATION 0.48
Montreal Cognitive Assessment (MoCA test)	22 units on a scale	22 units on a scale	22 units on a scale
National Institutes of Health Stroke Scale (NIHSS)	9 units on a scale	9.5 units on a scale	10 units on a scale
Percentage of Subjects Having Modified Rankin Scale (mRS) Scores 0-1 (Normal or Lower Degree of Disa	0 Participants	0 Participants	0 Participants
Percentage of Subjects Having Modified Rankin Scale (mRS) Scores >3 (Higher Degree of Disability)	152 Participants	304 Participants	152 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	13 Participants	29 Participants	16 Participants
Race (NIH/OMB) Black or African American	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	139 Participants	275 Participants	136 Participants
Region of Enrollment Kazakhstan	10 participants	20 participants	10 participants
Region of Enrollment Russia	132 participants	264 participants	132 participants
Region of Enrollment Uzbekistan	10 participants	20 participants	10 participants
Rivermead Mobility Index (RMI)	3 units on a scale	3 units on a scale	3 units on a scale
Sex: Female, Male Female	48 Participants	100 Participants	52 Participants
Sex: Female, Male Male	104 Participants	204 Participants	100 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	2 / 152	1 / 152
other Total, other adverse events	36 / 152	39 / 152
serious Total, serious adverse events	6 / 152	4 / 152

Outcome results

Primary

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).

Time frame: Baseline, Day 71

Arm	Measure	Value (MEAN)
Mexidol®	Change From Baseline in the Modified Rankin Scale (mRS) Scores at the End of the Course of Therapy	-2.45 score on a scale
Placebo	Change From Baseline in the Modified Rankin Scale (mRS) Scores at the End of the Course of Therapy	-2.01 score on a scale

Secondary

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).

Time frame: Baseline, Day 71