Safety and Efficacy of Sequential Therapy With Mexidol® in Patients With Chronic Cerebral Ischemia

International Multicentre Randomized, Double-blind, Placebo-controlled Adaptive Design Clinical Trial to Evaluate the Safety and Efficacy of Sequential Therapy With Mexidol® Solution for Intravenous and Intramuscular Administration, 50 mg/ml (RPC PHARMASOFT LLC, Russia) and Mexidol® FORTE 250 Film-coated Tablets, 250 mg (RPC PHARMASOFT LLC, Russia) in Patients With Chronic Cerebral Ischemia (MEMO)

The purpose of this study is to evaluate safety and efficacy of sequential treatment with Mexidol® in patients with chronic cerebral ischemia (CCI).

Chronic cerebral ischemia (CCI) is a cerebral vascular pathology caused by slow progressive diffuse disruption of blood flow to the brain with gradually increasing defects in its functioning. The activation of lipid peroxidation with the release of large amounts of active oxygen radicals plays the key role in the pathogenesis of ischemic disorders, which leads to the development of oxidative stress. However, traditional drug therapy, which is aimed at improving blood flow to the brain, is mainly based on drugs with psychostimulant component, and does not always prevent the increase of oxidative damage to the patients' body. That is why it is necessary to search for drugs that would correct these processes selectively. Mexidol contains ethylmethylhydroxypyridine succinate as an active substance and may be the drug of choice for the treatment of CCI patients.

Inclusion criteria:

1. Patients of either sex aged from 40 to 90 years inclusive
2. MoCA scale score of 25 and lower
3. Patients meeting the criteria for the diagnosis: Mild (moderate) cognitive impairment when assessed by DSM-5.
4. Chronic Cerebral Ischemia (ICD-10 code 167.8)
5. Foci of leukoaraiosis or "silent" brain infarction documented by MRI/CT performed within the past 12 months.
6. Patients who signed an informed consent to the study participation
7. History of progressive multifocal or diffuse brain disease from 1 to 5 years
8. Patients receiving background therapy with a fixed dose and combination of drugs during the previous month, including (if indicated): antiplatelet therapy, therapy of cerebral atherosclerosis and arterial hypertension, ischemic heart disease or other chronic diseases.
9. Negative pregnancy test
10. Patients who have agreed to use a reliable method of contraception during the study participation until completion (for women of childbearing potential, including partners of study participants).
11. Patients who are able to understand all study requirements and who have consented to all the limitations imposed by the study

Exclusion Criteria:

1. Inclusion by mistake (overlooked inclusion or non-inclusion criteria)
2. Investigator's or Sponsor's decision to exclude a participant from the study due to a clinically significant protocol deviation/violation.
3. Serious adverse events or adverse events that do not meet the criteria for seriousness but may, in the investigator's opinion, be detrimental to the health or well-being of a participant if they continue participation in the study.
4. Any adverse event (which may be unrelated to the investigational drug) requiring observations, procedures, and/or medications not approved by the clinical trial protocol.
5. Participant's refusal to continue participation in the study or their lack of discipline
6. Allergic reaction to the investigational drug that requires cancelling the treatment
7. Participant's desire to terminate their participation early for any reason.
8. Loss of contact with the patient followed by failure to attend the visit.
9. The need to take therapies prohibited by this protocol: nootropic drugs, ethylmethylhydroxypyridine succinate, trimetazidine or meldonium, drugs affecting the function of the autonomic nervous system and other drugs that may, in the investigator's opinion, distort the study results.
10. Pregnancy.