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

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).

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.

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.