Mexidol® Safety and Efficacy in Treatment of Hyperacute and Acute Ischemic Stroke

Exclusion Criteria79

• Hypersensitivity to ethylmethylhydroxypyridine succinate or any other components of the investigational product.
• Galactose intolerance, lactase deficiency, or glucose-galactose malabsorption.
• Inability to take oral medications.
• Contraindications or inability to undergo CT/MRI procedures (including, but not limited to: permanent cardiac pacemakers/neurostimulators; inner ear prosthesis, ferromagnetic or electronic middle ear implants, hemostatic clips, cardiac valve prostheses, or any other metal-containing structures; ferromagnetic fragments; insulin pumps; severe claustrophobia).
• Inability to undergo contrast-enhanced imaging for any reason.
• Patients who have received or are scheduled to receive thrombolytic therapy or thrombectomy for the current episode of ischemic stroke.
• Recurrent ischemic stroke.
• Direct signs of irreversible total occlusion of the internal carotid artery (ICA) system at the relevant level within the current episode of ischemic stroke (based on CT/MRI data).
• Absence of neuroimaging signs of acute ischemic brain injury.
• Presence of any of the following neuroimaging (CT/MRI) findings:
• Intracranial hemorrhage;
• Hemorrhagic transformation of the cerebral infarction;
• Subarachnoid hemorrhage;
• Brain tumor;
• Arteriovenous malformation (AVM);
• Brain abscess;
• Cerebral aneurysm;
• Edema of the infarct zone leading to brain structure displacement (malignant cerebral infarction).
• Lesion in the vertebrobasilar system.
• Any suspicion of subarachnoid hemorrhage (SAH) in the medical history or at the time of screening.
• History of hemorrhagic stroke or stroke of unspecified nature.
• Any known history of conditions associated with a bleeding tendency.
• Deep vein thrombosis (DVT) or pulmonary embolism (PE), or detection of a floating thrombus.
• Traumatic brain injury (TBI) within 6 months prior to screening.
• History of brain or spinal cord surgery within 5 years prior to study enrollment.
• Need for surgical intervention during participation in the clinical study.
• History of epilepsy.
• History of severe cognitive impairment, including dementia.
• Parkinson's disease.
• History of hereditary degenerative diseases of the Central Nervous System (CNS).
• History of demyelinating diseases of the nervous system.
• History of severe or global aphasia and/or clinical evidence of these conditions at screening.
• Myocardial infarction within 3 months prior to screening.
• NYHA Class III-IV chronic heart failure at the time of screening.
• Unstable angina pectoris at the time of screening.
• SBP ≥ 200 mmHg and/or DBP ≥ 100 mmHg at the time of screening.
• History of Stage III-IV Chronic Obstructive Pulmonary Disease (COPD).
• Uncontrolled diabetes mellitus.
• Renal impairment (creatinine clearance < 50 mL/min calculated by the Cockcroft-Gault formula) at the time of screening.
• Hepatic impairment (AST and/or ALT ≥ 2 × ULN and/or total bilirubin ≥ 1.5 × ULN) at the time of screening.
• History of HIV, syphilis, hepatitis B, and/or hepatitis C.
• Acute infectious diseases (influenza, upper respiratory tract infections, etc.) within 4 weeks prior to screening.
• Use of prohibited medications or other drugs that, in the investigator's opinion, may interfere with the study results within 30 days prior to screening, or the anticipated need for such medications during the patient's participation in the study.
• Use of medications based on ethylmethylhydroxypyridine succinate for 3 or more consecutive days within 2 weeks prior to randomization.
• Systemic autoimmune diseases or vascular collagenoses requiring prior or current treatment with systemic corticosteroids, cytostatics, or other immunosuppressants.
• History of malignant neoplasms, except for patients who have been disease-free for the past 5 years, or those with completely cured basal cell carcinoma of the skin, or completely cured carcinoma in situ.
• Other severe, decompensated, or unstable medical conditions that, in the investigator's opinion, are life-threatening, adversely affect the patient's prognosis, or preclude safe participation in the study.
• Life expectancy of less than 6 months.
• Unwillingness or inability of the patient to comply with the study protocol procedures (in the investigator's opinion).
• Pregnancy or breastfeeding (for women).
• History of alcoholism, drug addiction, or substance abuse and/or presence of these conditions at screening.
• History of schizophrenia, schizoaffective disorder, bipolar disorder, or other psychiatric disorders.
• Participation in another clinical trial within 3 months prior to study enrollment.
• Any other conditions that, in the investigator's opinion, preclude the patient's inclusion in the study.
• Acute or chronic diseases of the cardiovascular, bronchopulmonary, endocrine, and nervous systems, including organic central nervous system (CNS) disorders, as well as gastrointestinal (GI), hepatic, renal, and hematological diseases.
• Galactose intolerance, lactase deficiency, or glucose-galactose malabsorption.
• Any deviations from normal values during laboratory and/or instrumental examinations.
• Inability to undergo blood sampling (e.g., due to compromised skin integrity at venipuncture sites).
• History of intracranial hemorrhage of any etiology.
• Hemophilia or other blood clotting disorders (including hypocoagulation states) and hemorrhagic diatheses.
• Active bleeding of any etiology at the time of screening.
• Decreased circulating blood volume (due to a salt-free diet, vomiting, or diarrhea).
• Blood donation or blood loss (≥ 450 mL of blood or plasma) within 3 months prior to screening.
• Any surgical procedures performed within 30 days prior to screening or planned during the study period.
• Acute infectious diseases, as well as fungal infections, within 4 weeks prior to the start of screening.
• Vaccination planned during the study or administered within 14 days prior to the start of screening.
• Regular use of medications, including herbal and homeopathic remedies, vitamins, and/or dietary supplements, within 4 weeks prior to the start of screening.
• Alcohol consumption within 72 hours prior to the start of screening.
• Use of medications with a significant effect on hemodynamics and/or liver function (e.g., barbiturates, omeprazole, cimetidine, etc.), injectable or oral hormonal contraceptives, subcutaneous hormonal implants, or intrauterine systems within 2 months prior to screening procedures.
• Adherence to a specific diet (e.g., vegetarian, vegan, or low-salt diet) within 2 months prior to the start of screening.
• Specific lifestyle factors (e.g., night-shift work, extreme physical exertion) within 2 months prior to the start of screening.
• History of alcohol consumption exceeding 10 units per week (1 unit is equivalent to 500 mL of beer, 200 mL of wine, or 50 mL of spirits), or a medical history of alcoholism, drug addiction, or substance abuse.
• Smoking at the time of the screening visit.
• Piercing, tattoos, or permanent makeup performed within 1 month prior to screening or planned during the study.
• Mental, physical, or other reasons preventing the volunteer from adequately assessing their behavior and correctly following the Study Protocol requirements.
• Inability or unwillingness to comply with required contraceptive measures.
• Pregnancy (confirmed by a positive pregnancy test) or breastfeeding at the time of screening25.
• Participation in another clinical trial within 3 months prior to the start of screening.
• Other reasons that, in the investigator's opinion, preclude the volunteer's participation in this study.