Chronic Cerebral Ischemia
Conditions
Keywords
Chronic Cerebral Ischemia, CCI, Ischemia, Cerebral, Brain, Stroke, Cognitive, Neurobehavioral Manifestations, Neuroprotection, Mexidol, Ethylmethylhydroxypyridine Succinate, Cerebrovascular Disorders, Antioxidant Therapy, Stroke Recovery, Central Nervous System Disorders, Chronic Brain Hypoxia, Post-stroke Cognitive Impairment, Cognitive Impairment, Neurodegenerative, Neurodegenerative Processes, Neurological Rehabilitation, Oxidative Stress, Oxidative Stress Reduction, Energy Metabolism Enhancement, Central Nervous System, Cerebral Hypoxia
Brief summary
The purpose of this study is to evaluate safety and efficacy of sequential treatment with Mexidol® in patients with chronic cerebral ischemia (CCI).
Detailed description
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.
Interventions
DRUGMexidol
50 mg/ml IV solution, 250 mg tablets
DRUGPlacebo
Placebo IV solution, Placebo tablets
Sponsors
Pharmasoft
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to 90 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Score of Montreal Cognitive Assessment (MoCA) at Visit 5 in Comparison With Reference Score at Visit 0 | Day 75+2 (Visit 5) compared with the baseline level (Visit 0, 7 days before treatment) | The Montreal Cognitive Assessment (MoCA) is used to measure the degree of cognitive impairment in patients with CCI. MoCA scores range between 0 and 30. A score of 26 or over is considered to be normal. Higher score than shown at Visit 0 is expected after treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Patients' Quality of Life Assessed With SF-36 Questionnaire (Physical Health) | Day 14 (Visit 2), Day 44±2 (Visit 4), Day 75+2 (Visit 5) compared with the baseline level (Visit 1, Day 1 of treatment) | The SF-36 questionnaire is used between Visit 1 and Visits 2, 4, 5. The SF-36 questionnaire consists of eight scales yielding two summary measures: physical and mental health. To score the SF-36, scales are standardized with a scoring algorithm or by the SF-36v2 scoring software to obtain a score ranging from 0 to 100. Higher scores indicate better health status, and a mean score of 50 has been articulated as a normative value for all scales. |
| Changes in Patients' Quality of Life Assessed With SF-36 Questionnaire (Mental Health) | Day 14 (Visit 2), Day 44±2 (Visit 4), Day 75+2 (Visit 5) compared with the baseline level (Visit 1, Day 1 of treatment) | The SF-36 questionnaire is used between Visit 1 and Visits 2, 4, 5. The SF-36 questionnaire consists of eight scales yielding two summary measures: physical and mental health. To score the SF-36, scales are standardized with a scoring algorithm or by the SF-36v2 scoring software to obtain a score ranging from 0 to 100. Higher scores indicate better health status, and a mean score of 50 has been articulated as a normative value for all scales. |
| Changes in the Severity of Asthenia Assessed With the Multidimensional Fatigue Inventory (MFI-20) | Day 14 (Visit 2), Day 44±2 (Visit 4), Day 75+2 (Visit 5) compared with the baseline level (Visit 1, Day 1 of treatment) | The Multidimensional Fatigue Inventory (MFI-20) is used between Visit 1 and Visits 2, 4, 5. MFI-20 is a 20-item self-administered questionnaire designed to measure fatigue in five four-item subscales: General fatigue, Physical fatigue, Reduced activity, Reduced motivation and Mental fatigue. MFI-20 has an even proportion of positively and negatively worded items that are rated on a 5-point Likert scale. Subscale scores (range 4-20) are calculated as the sum of item ratings and a total fatigue score (range 20-100) is calculated as the sum of subscale scores. Higher scores indicate a higher level of fatigue. |
| Changes in the Anxiety Level According to the Beck Anxiety Inventory | Day 14 (Visit 2), Day 44±2 (Visit 4), Day 75+2 (Visit 5) compared with the baseline level (Visit 1, Day 1 of treatment) | The Beck Anxiety Inventory (BAI) consists of 21 self-reported items (four-point scale) used to assess the intensity of physical and cognitive anxiety symptoms during the past week. Scores may range from 0 to 63: minimal anxiety levels (0-7), mild anxiety (8-15), moderate anxiety (16-25), and severe anxiety (26-63). |
| Changes in the Severity of Cognitive Impairment Assessed With the Montreal Cognitive Assessment Scale Between Visit 0 and Visits 2 and 4 | Day 14 (Visit 2) and Day 44±2 (Visit 4) compared with the baseline level (Visit 0, 7 days before treatment) | The Montreal Cognitive Assessment (MoCA) is used to measure the changes in the severity of cognitive impairment at Visits 2 and 4 in comparison to Visit 0. MoCA scores range between 0 and 30. A score of 26 or over is considered to be normal. Higher score than shown at Visit 0 is expected. |
| Changes in Cognitive Impairment Assessed With Digit Symbol Substitution Test | Day 14 (Visit 2), Day 44±2 (Visit 4), Day 75+2 (Visit 5) compared with the baseline level (Visit 1, Day 1 of treatment) | The Digit Symbol Substitution Test is used between Visit 1 and Visits 2, 4, 5. The DSST is used to measure attention, processing speed and executive function. It is a pencil and paper test of psychomotor performance in which the subject is given a key grid of numbers and matching symbols and a test section with numbers and empty boxes. The test consists of filling as many empty boxes as possible with a symbol matching each number. The score is the number of correct number-symbol matches achieved in 90 s. Scores range from 0 to 100, with higher scores indicating higher cognitive function. |
| Motor Changes Assessed With the Tinetti Test | Day 14 (Visit 2), Day 44±2 (Visit 4), Day 75+2 (Visit 5) compared with the baseline level (Visit 1, Day 1 of treatment) | The Tinetti test is used between Visit 1 and Visits 2, 4, 5. The Tinetti test is a clinical test for the assessment of balance and gait. It has a gait score and a balance score using a 3-point ordinal scale of 0, 1 and 2. Gait is scored over 12 and balance is scored over 16 totalling 28. The lower the score on the Tinetti test, the higher the risk of falling. Tinetti test score equal or less than 18 shows high risk of fall, 19-23 scores show moderate risk of fall, and score equal or higher than 24 shows low risk of fall. Thus, min value is 0, max value is 28, higher scores mean a better outcome. |
| Change in Global Illness Severity Assessed With the Clinical Global Impressions Scale at Visit 5 Compared to Baseline Measure | Day 75+2 (Visit 5) | The Clinical Global Impressions Scale is a standardized assessment tool used to rate the severity of illness, change over time, and efficacy of medication. The interpretation of scores is as follows: 00 - Not assessed 01 - Vast improvement. Side effects - None. 03 - Vast improvement. Side effects - Significantly interfere with patient's therapeutic patient's functioning 04 - Vast improvement. Side effects - outweights therapeutic effect 05 - Decided improvement. Side effects - none 09 - Slight improvement. Side effects - none 10 - Slight improvement. Side effects - do not significantly interfere with patient's functioning 13 - Slight improvement. Side effects - none |
| Autonomic Changes According to the A.M.Wein's Questionnaire | Day 14 (Visit 2), Day 44±2 (Visit 4), Day 75+2 (Visit 5) compared with the baseline level (Visit 1, Day 1 of treatment) | The A.M.Wein's questionnaire is used between Visit 1 and Visit 2, 4, 5. It includes 11 main signs of autonomic disorders. Each autonomic symptom is assessed using scores from 7 to 3, then the scores are summed. Scores may range from 0 to 60, higher scores mean a worse outcome. The total sum of the scores in healthy individuals should be 0-14 scores. 15-29 scores are indicative of moderate vegetative dystonia syndrome, 30 and more scores are indicative of severe vegetative dystonia syndrome. |
Countries
Russia, Uzbekistan
Participant flow
Recruitment details
Participants were recruited based on protocol requirements at 15 clinical sites between November 2019 and December 2020. The first participant was enrolled on 05 November, 2019 and the last participant was enrolled on 14 September, 2020.
Pre-assignment details
Of 330 screened participants, 318 met inclusion criteria and were randomized to treatment.
Participants by arm
| Arm | Count |
|---|---|
| Main (Mexidol) Participants received Mexidol IV 500 mg (10 ml) once daily for 14 days, then Mexidol FORTE 250 orally 250 mg 1 tablet 3 times a day for 60 days | 159 |
| Control (Placebo) Participants received Mexidol Placebo matching Mexidol IV 500 mg (10 ml) once daily for 14 days, then Mexidol Placebo matching Mexidol FORTE 250 orally 250 mg 1 tablet 3 times a day for 60 days | 159 |
| Total | 318 |
Baseline characteristics
| Characteristic | Main (Mexidol) | Control (Placebo) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 55 Participants | 60 Participants | 115 Participants |
| Age, Categorical Between 18 and 65 years | 104 Participants | 99 Participants | 203 Participants |
| Age, Continuous | 60.08 Years STANDARD_DEVIATION 9.86 | 60.73 Years STANDARD_DEVIATION 9.03 | 60.44 Years STANDARD_DEVIATION 9.59 |
| A.M.Wein's questionnaire scores at Visit 1 (Day 1 of treatment) | 26.59 score on a scale STANDARD_DEVIATION 13.63 | 26.28 score on a scale STANDARD_DEVIATION 12.7 | 26.43 score on a scale STANDARD_DEVIATION 13.13 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 10 Participants | 8 Participants | 18 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 | 149 Participants | 151 Participants | 300 Participants |
| Region of Enrollment Russia | 151 Participants | 151 Participants | 302 Participants |
| Region of Enrollment Uzbekistan | 8 Participants | 8 Participants | 16 Participants |
| Sex: Female, Male Female | 119 Participants | 121 Participants | 240 Participants |
| Sex: Female, Male Male | 40 Participants | 38 Participants | 78 Participants |
| The Beck Anxiety Inventory scores at Visit 1 (Day 1 of treatment) | 11.85 score on a scale STANDARD_DEVIATION 8.11 | 11.23 score on a scale STANDARD_DEVIATION 8.54 | 11.51 score on a scale STANDARD_DEVIATION 8.33 |
| The Digit Symbol Substitution Test scores at Visit 1 (Day 1 of treatment) | 32.84 score on a scale STANDARD_DEVIATION 10.94 | 33.87 score on a scale STANDARD_DEVIATION 12.24 | 33.36 score on a scale STANDARD_DEVIATION 11.63 |
| The Montreal Cognitive Assessment scores at Visit 0 (7 days before treatment) | 21.53 score on a scale STANDARD_DEVIATION 2.27 | 21.80 score on a scale STANDARD_DEVIATION 1.96 | 21.67 score on a scale STANDARD_DEVIATION 2.13 |
| The Multidimensional Fatigue Inventory scores at Visit 1 (Day 1 of treatment) | 59.77 score on a scale STANDARD_DEVIATION 13.35 | 58.79 score on a scale STANDARD_DEVIATION 13.78 | 59.25 score on a scale STANDARD_DEVIATION 13.55 |
| The SF-36 questionnaire scores at Visit 1 (Day 1 of treatment) The SF-36 questionnaire: mental health | 44.12 score on a scale STANDARD_DEVIATION 9.18 | 44.95 score on a scale STANDARD_DEVIATION 9.2 | 44.51 score on a scale STANDARD_DEVIATION 9.18 |
| The SF-36 questionnaire scores at Visit 1 (Day 1 of treatment) The SF-36 questionnaire: physical health | 44.21 score on a scale STANDARD_DEVIATION 8.58 | 44.12 score on a scale STANDARD_DEVIATION 7.92 | 44.21 score on a scale STANDARD_DEVIATION 8.28 |
| The Tinetti test scores at Visit 1 (Day 1 of treatment) | 32.64 score on a scale STANDARD_DEVIATION 5.3 | 33.30 score on a scale STANDARD_DEVIATION 5.23 | 32.99 score on a scale STANDARD_DEVIATION 5.27 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 159 | 0 / 159 |
| other Total, other adverse events | 19 / 159 | 32 / 159 |
| serious Total, serious adverse events | 0 / 159 | 0 / 159 |
Outcome results
Primary
Mean Score of Montreal Cognitive Assessment (MoCA) at Visit 5 in Comparison With Reference Score at Visit 0
The Montreal Cognitive Assessment (MoCA) is used to measure the degree of cognitive impairment in patients with CCI. MoCA scores range between 0 and 30. A score of 26 or over is considered to be normal. Higher score than shown at Visit 0 is expected after treatment.
Time frame: Day 75+2 (Visit 5) compared with the baseline level (Visit 0, 7 days before treatment)
Population: The efficacy analysis was performed for ITT-population excluding participant No. 098 whose data after the randomization visit are missing.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Main (Mexidol) | Mean Score of Montreal Cognitive Assessment (MoCA) at Visit 5 in Comparison With Reference Score at Visit 0 | MoCA Scores at Visit 5 | 25.72 score on a scale | Standard Deviation 2.47 |
| Main (Mexidol) | Mean Score of Montreal Cognitive Assessment (MoCA) at Visit 5 in Comparison With Reference Score at Visit 0 | Difference in comparison with Visit 0 | 4.22 score on a scale | Standard Deviation 2.59 |
| Control (Placebo) | Mean Score of Montreal Cognitive Assessment (MoCA) at Visit 5 in Comparison With Reference Score at Visit 0 | MoCA Scores at Visit 5 | 23.95 score on a scale | Standard Deviation 2.58 |
| Control (Placebo) | Mean Score of Montreal Cognitive Assessment (MoCA) at Visit 5 in Comparison With Reference Score at Visit 0 | Difference in comparison with Visit 0 | 2.17 score on a scale | Standard Deviation 2.2 |
Secondary
Autonomic Changes According to the A.M.Wein's Questionnaire
The A.M.Wein's questionnaire is used between Visit 1 and Visit 2, 4, 5. It includes 11 main signs of autonomic disorders. Each autonomic symptom is assessed using scores from 7 to 3, then the scores are summed. Scores may range from 0 to 60, higher scores mean a worse outcome. The total sum of the scores in healthy individuals should be 0-14 scores. 15-29 scores are indicative of moderate vegetative dystonia syndrome, 30 and more scores are indicative of severe vegetative dystonia syndrome.
Time frame: Day 14 (Visit 2), Day 44±2 (Visit 4), Day 75+2 (Visit 5) compared with the baseline level (Visit 1, Day 1 of treatment)
Population: The efficacy analysis was performed for ITT-population excluding participant No. 098 whose data after the randomization visit are missing.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Main (Mexidol) | Autonomic Changes According to the A.M.Wein's Questionnaire | Wein's questionnaire, Visit 2 | 23.58 score on a scale | Standard Deviation 13.68 |
| Main (Mexidol) | Autonomic Changes According to the A.M.Wein's Questionnaire | Difference at Visit 2 in comparison with Visit 1 | -3.01 score on a scale | Standard Deviation 7.71 |
| Main (Mexidol) | Autonomic Changes According to the A.M.Wein's Questionnaire | Wein's questionnaire, Visit 4 | 21.37 score on a scale | Standard Deviation 13.8 |
| Main (Mexidol) | Autonomic Changes According to the A.M.Wein's Questionnaire | Difference at Visit 4 in comparison with Visit 1 | -5.23 score on a scale | Standard Deviation 9.19 |
| Main (Mexidol) | Autonomic Changes According to the A.M.Wein's Questionnaire | Wein's questionnaire, Visit 5 | 19.70 score on a scale | Standard Deviation 13.92 |
| Main (Mexidol) | Autonomic Changes According to the A.M.Wein's Questionnaire | Difference at Visit 5 in comparison with Visit 1 | -6.76 score on a scale | Standard Deviation 10.94 |
| Control (Placebo) | Autonomic Changes According to the A.M.Wein's Questionnaire | Wein's questionnaire, Visit 5 | 22.01 score on a scale | Standard Deviation 13.07 |
| Control (Placebo) | Autonomic Changes According to the A.M.Wein's Questionnaire | Wein's questionnaire, Visit 2 | 24.11 score on a scale | Standard Deviation 12.61 |
| Control (Placebo) | Autonomic Changes According to the A.M.Wein's Questionnaire | Difference at Visit 4 in comparison with Visit 1 | -3.42 score on a scale | Standard Deviation 10.23 |
| Control (Placebo) | Autonomic Changes According to the A.M.Wein's Questionnaire | Difference at Visit 2 in comparison with Visit 1 | -2.18 score on a scale | Standard Deviation 8.01 |
| Control (Placebo) | Autonomic Changes According to the A.M.Wein's Questionnaire | Difference at Visit 5 in comparison with Visit 1 | -4.30 score on a scale | Standard Deviation 10.81 |
| Control (Placebo) | Autonomic Changes According to the A.M.Wein's Questionnaire | Wein's questionnaire, Visit 4 | 22.89 score on a scale | Standard Deviation 12.61 |
Secondary
Change in Global Illness Severity Assessed With the Clinical Global Impressions Scale at Visit 5 Compared to Baseline Measure
The Clinical Global Impressions Scale is a standardized assessment tool used to rate the severity of illness, change over time, and efficacy of medication. The interpretation of scores is as follows: 00 - Not assessed 01 - Vast improvement. Side effects - None. 03 - Vast improvement. Side effects - Significantly interfere with patient's therapeutic patient's functioning 04 - Vast improvement. Side effects - outweights therapeutic effect 05 - Decided improvement. Side effects - none 09 - Slight improvement. Side effects - none 10 - Slight improvement. Side effects - do not significantly interfere with patient's functioning 13 - Slight improvement. Side effects - none
Time frame: Day 75+2 (Visit 5)
Population: The analysis was performed for the PP-population (312 participants).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Main (Mexidol) | Change in Global Illness Severity Assessed With the Clinical Global Impressions Scale at Visit 5 Compared to Baseline Measure | 04 | 0 Participants |
| Main (Mexidol) | Change in Global Illness Severity Assessed With the Clinical Global Impressions Scale at Visit 5 Compared to Baseline Measure | 09 | 54 Participants |
| Main (Mexidol) | Change in Global Illness Severity Assessed With the Clinical Global Impressions Scale at Visit 5 Compared to Baseline Measure | 03 | 1 Participants |
| Main (Mexidol) | Change in Global Illness Severity Assessed With the Clinical Global Impressions Scale at Visit 5 Compared to Baseline Measure | 10 | 3 Participants |
| Main (Mexidol) | Change in Global Illness Severity Assessed With the Clinical Global Impressions Scale at Visit 5 Compared to Baseline Measure | 05 | 39 Participants |
| Main (Mexidol) | Change in Global Illness Severity Assessed With the Clinical Global Impressions Scale at Visit 5 Compared to Baseline Measure | 13 | 15 Participants |
| Main (Mexidol) | Change in Global Illness Severity Assessed With the Clinical Global Impressions Scale at Visit 5 Compared to Baseline Measure | 01 | 45 Participants |
| Control (Placebo) | Change in Global Illness Severity Assessed With the Clinical Global Impressions Scale at Visit 5 Compared to Baseline Measure | 13 | 75 Participants |
| Control (Placebo) | Change in Global Illness Severity Assessed With the Clinical Global Impressions Scale at Visit 5 Compared to Baseline Measure | 01 | 7 Participants |
| Control (Placebo) | Change in Global Illness Severity Assessed With the Clinical Global Impressions Scale at Visit 5 Compared to Baseline Measure | 03 | 0 Participants |
| Control (Placebo) | Change in Global Illness Severity Assessed With the Clinical Global Impressions Scale at Visit 5 Compared to Baseline Measure | 04 | 1 Participants |
| Control (Placebo) | Change in Global Illness Severity Assessed With the Clinical Global Impressions Scale at Visit 5 Compared to Baseline Measure | 05 | 16 Participants |
| Control (Placebo) | Change in Global Illness Severity Assessed With the Clinical Global Impressions Scale at Visit 5 Compared to Baseline Measure | 09 | 56 Participants |
| Control (Placebo) | Change in Global Illness Severity Assessed With the Clinical Global Impressions Scale at Visit 5 Compared to Baseline Measure | 10 | 0 Participants |
Secondary
Changes in Cognitive Impairment Assessed With Digit Symbol Substitution Test
The Digit Symbol Substitution Test is used between Visit 1 and Visits 2, 4, 5. The DSST is used to measure attention, processing speed and executive function. It is a pencil and paper test of psychomotor performance in which the subject is given a key grid of numbers and matching symbols and a test section with numbers and empty boxes. The test consists of filling as many empty boxes as possible with a symbol matching each number. The score is the number of correct number-symbol matches achieved in 90 s. Scores range from 0 to 100, with higher scores indicating higher cognitive function.
Time frame: Day 14 (Visit 2), Day 44±2 (Visit 4), Day 75+2 (Visit 5) compared with the baseline level (Visit 1, Day 1 of treatment)
Population: The efficacy analysis was performed for ITT-population excluding participant No. 098 whose data after the randomization visit are missing.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Main (Mexidol) | Changes in Cognitive Impairment Assessed With Digit Symbol Substitution Test | DSST, Visit 2 | 36.94 score on a scale | Standard Deviation 10.82 |
| Main (Mexidol) | Changes in Cognitive Impairment Assessed With Digit Symbol Substitution Test | Difference at Visit 2 in comparison with Visit 1 | 4.11 score on a scale | Standard Deviation 6.63 |
| Main (Mexidol) | Changes in Cognitive Impairment Assessed With Digit Symbol Substitution Test | DSST, Visit 4 | 39.80 score on a scale | Standard Deviation 10.78 |
| Main (Mexidol) | Changes in Cognitive Impairment Assessed With Digit Symbol Substitution Test | Difference at Visit 4 in comparison with Visit 1 | 6.91 score on a scale | Standard Deviation 8.1 |
| Main (Mexidol) | Changes in Cognitive Impairment Assessed With Digit Symbol Substitution Test | DSST, Visit 5 | 42.72 score on a scale | Standard Deviation 12.53 |
| Main (Mexidol) | Changes in Cognitive Impairment Assessed With Digit Symbol Substitution Test | Difference at Visit 5 in comparison with Visit 1 | 9.84 score on a scale | Standard Deviation 10.5 |
| Control (Placebo) | Changes in Cognitive Impairment Assessed With Digit Symbol Substitution Test | DSST, Visit 5 | 39.05 score on a scale | Standard Deviation 12.36 |
| Control (Placebo) | Changes in Cognitive Impairment Assessed With Digit Symbol Substitution Test | DSST, Visit 2 | 36.33 score on a scale | Standard Deviation 11.84 |
| Control (Placebo) | Changes in Cognitive Impairment Assessed With Digit Symbol Substitution Test | Difference at Visit 4 in comparison with Visit 1 | 4.24 score on a scale | Standard Deviation 8.77 |
| Control (Placebo) | Changes in Cognitive Impairment Assessed With Digit Symbol Substitution Test | Difference at Visit 2 in comparison with Visit 1 | 2.61 score on a scale | Standard Deviation 7.18 |
| Control (Placebo) | Changes in Cognitive Impairment Assessed With Digit Symbol Substitution Test | Difference at Visit 5 in comparison with Visit 1 | 5.40 score on a scale | Standard Deviation 10.15 |
| Control (Placebo) | Changes in Cognitive Impairment Assessed With Digit Symbol Substitution Test | DSST, Visit 4 | 37.89 score on a scale | Standard Deviation 11.78 |
Secondary
Changes in Patients' Quality of Life Assessed With SF-36 Questionnaire (Mental Health)
The SF-36 questionnaire is used between Visit 1 and Visits 2, 4, 5. The SF-36 questionnaire consists of eight scales yielding two summary measures: physical and mental health. To score the SF-36, scales are standardized with a scoring algorithm or by the SF-36v2 scoring software to obtain a score ranging from 0 to 100. Higher scores indicate better health status, and a mean score of 50 has been articulated as a normative value for all scales.
Time frame: Day 14 (Visit 2), Day 44±2 (Visit 4), Day 75+2 (Visit 5) compared with the baseline level (Visit 1, Day 1 of treatment)
Population: The efficacy analysis was performed for ITT-population excluding participant No. 098 whose data after the randomization visit are missing.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Main (Mexidol) | Changes in Patients' Quality of Life Assessed With SF-36 Questionnaire (Mental Health) | SF-36: mental health (Visit 2) | 46.64 score on a scale | Standard Deviation 8.91 |
| Main (Mexidol) | Changes in Patients' Quality of Life Assessed With SF-36 Questionnaire (Mental Health) | Difference at Visit 2 in comparison with Visit 1 | 2.52 score on a scale | Standard Deviation 6.75 |
| Main (Mexidol) | Changes in Patients' Quality of Life Assessed With SF-36 Questionnaire (Mental Health) | SF-36: mental health (Visit 4) | 48.46 score on a scale | Standard Deviation 8.74 |
| Main (Mexidol) | Changes in Patients' Quality of Life Assessed With SF-36 Questionnaire (Mental Health) | Difference at Visit 4 in comparison with Visit 1 | 4.30 score on a scale | Standard Deviation 7.85 |
| Main (Mexidol) | Changes in Patients' Quality of Life Assessed With SF-36 Questionnaire (Mental Health) | SF-36: mental health (Visit 5) | 50.51 score on a scale | Standard Deviation 7.96 |
| Main (Mexidol) | Changes in Patients' Quality of Life Assessed With SF-36 Questionnaire (Mental Health) | Difference at Visit 5 in comparison with Visit 1 | 6.36 score on a scale | Standard Deviation 8.14 |
| Control (Placebo) | Changes in Patients' Quality of Life Assessed With SF-36 Questionnaire (Mental Health) | SF-36: mental health (Visit 5) | 48.40 score on a scale | Standard Deviation 8.77 |
| Control (Placebo) | Changes in Patients' Quality of Life Assessed With SF-36 Questionnaire (Mental Health) | SF-36: mental health (Visit 2) | 46.40 score on a scale | Standard Deviation 9.16 |
| Control (Placebo) | Changes in Patients' Quality of Life Assessed With SF-36 Questionnaire (Mental Health) | Difference at Visit 4 in comparison with Visit 1 | 2.45 score on a scale | Standard Deviation 6.46 |
| Control (Placebo) | Changes in Patients' Quality of Life Assessed With SF-36 Questionnaire (Mental Health) | Difference at Visit 2 in comparison with Visit 1 | 1.49 score on a scale | Standard Deviation 4.7 |
| Control (Placebo) | Changes in Patients' Quality of Life Assessed With SF-36 Questionnaire (Mental Health) | Difference at Visit 5 in comparison with Visit 1 | 3.46 score on a scale | Standard Deviation 8.05 |
| Control (Placebo) | Changes in Patients' Quality of Life Assessed With SF-36 Questionnaire (Mental Health) | SF-36: mental health (Visit 4) | 47.38 score on a scale | Standard Deviation 9.14 |
Secondary
Changes in Patients' Quality of Life Assessed With SF-36 Questionnaire (Physical Health)
The SF-36 questionnaire is used between Visit 1 and Visits 2, 4, 5. The SF-36 questionnaire consists of eight scales yielding two summary measures: physical and mental health. To score the SF-36, scales are standardized with a scoring algorithm or by the SF-36v2 scoring software to obtain a score ranging from 0 to 100. Higher scores indicate better health status, and a mean score of 50 has been articulated as a normative value for all scales.
Time frame: Day 14 (Visit 2), Day 44±2 (Visit 4), Day 75+2 (Visit 5) compared with the baseline level (Visit 1, Day 1 of treatment)
Population: The efficacy analysis was performed for ITT-population excluding participant No. 098 whose data after the randomization visit are missing.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Main (Mexidol) | Changes in Patients' Quality of Life Assessed With SF-36 Questionnaire (Physical Health) | SF-36: physical health (Visit 2) | 44.81 score on a scale | Standard Deviation 8.28 |
| Main (Mexidol) | Changes in Patients' Quality of Life Assessed With SF-36 Questionnaire (Physical Health) | Difference at Visit 2 in comparison with Visit 1 | 0.60 score on a scale | Standard Deviation 5.29 |
| Main (Mexidol) | Changes in Patients' Quality of Life Assessed With SF-36 Questionnaire (Physical Health) | SF-36: physical health (Visit 4) | 46.52 score on a scale | Standard Deviation 7.9 |
| Main (Mexidol) | Changes in Patients' Quality of Life Assessed With SF-36 Questionnaire (Physical Health) | Difference at Visit 4 in comparison with Visit 1 | 2.35 score on a scale | Standard Deviation 6.07 |
| Main (Mexidol) | Changes in Patients' Quality of Life Assessed With SF-36 Questionnaire (Physical Health) | SF-36: physical health (Visit 5) | 47.31 score on a scale | Standard Deviation 7.96 |
| Main (Mexidol) | Changes in Patients' Quality of Life Assessed With SF-36 Questionnaire (Physical Health) | Difference at Visit 5 in comparison with Visit 1 | 3.08 score on a scale | Standard Deviation 6.7 |
| Control (Placebo) | Changes in Patients' Quality of Life Assessed With SF-36 Questionnaire (Physical Health) | SF-36: physical health (Visit 5) | 46.27 score on a scale | Standard Deviation 7.77 |
| Control (Placebo) | Changes in Patients' Quality of Life Assessed With SF-36 Questionnaire (Physical Health) | SF-36: physical health (Visit 2) | 44.94 score on a scale | Standard Deviation 7.83 |
| Control (Placebo) | Changes in Patients' Quality of Life Assessed With SF-36 Questionnaire (Physical Health) | Difference at Visit 4 in comparison with Visit 1 | 2.03 score on a scale | Standard Deviation 5.6 |
| Control (Placebo) | Changes in Patients' Quality of Life Assessed With SF-36 Questionnaire (Physical Health) | Difference at Visit 2 in comparison with Visit 1 | 0.79 score on a scale | Standard Deviation 4.53 |
| Control (Placebo) | Changes in Patients' Quality of Life Assessed With SF-36 Questionnaire (Physical Health) | Difference at Visit 5 in comparison with Visit 1 | 2.23 score on a scale | Standard Deviation 5.79 |
| Control (Placebo) | Changes in Patients' Quality of Life Assessed With SF-36 Questionnaire (Physical Health) | SF-36: physical health (Visit 4) | 46.07 score on a scale | Standard Deviation 7.78 |
Secondary
Changes in the Anxiety Level According to the Beck Anxiety Inventory
The Beck Anxiety Inventory (BAI) consists of 21 self-reported items (four-point scale) used to assess the intensity of physical and cognitive anxiety symptoms during the past week. Scores may range from 0 to 63: minimal anxiety levels (0-7), mild anxiety (8-15), moderate anxiety (16-25), and severe anxiety (26-63).
Time frame: Day 14 (Visit 2), Day 44±2 (Visit 4), Day 75+2 (Visit 5) compared with the baseline level (Visit 1, Day 1 of treatment)
Population: The efficacy analysis was performed for ITT-population excluding participant No. 098 whose data after the randomization visit are missing.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Main (Mexidol) | Changes in the Anxiety Level According to the Beck Anxiety Inventory | Difference at Visit 2 in comparison with Visit 1 | -1.88 score on a scale | Standard Deviation 5.1 |
| Main (Mexidol) | Changes in the Anxiety Level According to the Beck Anxiety Inventory | Difference at Visit 4 in comparison with Visit 1 | -3.77 score on a scale | Standard Deviation 5.09 |
| Main (Mexidol) | Changes in the Anxiety Level According to the Beck Anxiety Inventory | BAI scores at Visit 2 | 9.97 score on a scale | Standard Deviation 8.1 |
| Main (Mexidol) | Changes in the Anxiety Level According to the Beck Anxiety Inventory | BAI scores at Visit 5 | 7.07 score on a scale | Standard Deviation 6.42 |
| Main (Mexidol) | Changes in the Anxiety Level According to the Beck Anxiety Inventory | BAI scores at Visit 4 | 8.10 score on a scale | Standard Deviation 7.04 |
| Main (Mexidol) | Changes in the Anxiety Level According to the Beck Anxiety Inventory | Difference at Visit 5 in comparison with Visit 1 | -4.70 score on a scale | Standard Deviation 5.49 |
| Control (Placebo) | Changes in the Anxiety Level According to the Beck Anxiety Inventory | BAI scores at Visit 4 | 9.14 score on a scale | Standard Deviation 7.13 |
| Control (Placebo) | Changes in the Anxiety Level According to the Beck Anxiety Inventory | BAI scores at Visit 2 | 10.08 score on a scale | Standard Deviation 7.23 |
| Control (Placebo) | Changes in the Anxiety Level According to the Beck Anxiety Inventory | Difference at Visit 2 in comparison with Visit 1 | -1.11 score on a scale | Standard Deviation 5.54 |
| Control (Placebo) | Changes in the Anxiety Level According to the Beck Anxiety Inventory | Difference at Visit 5 in comparison with Visit 1 | -2.26 score on a scale | Standard Deviation 7.1 |
| Control (Placebo) | Changes in the Anxiety Level According to the Beck Anxiety Inventory | Difference at Visit 4 in comparison with Visit 1 | -2.02 score on a scale | Standard Deviation 5.98 |
| Control (Placebo) | Changes in the Anxiety Level According to the Beck Anxiety Inventory | BAI scores at Visit 5 | 8.90 score on a scale | Standard Deviation 7.15 |
Secondary
Changes in the Severity of Asthenia Assessed With the Multidimensional Fatigue Inventory (MFI-20)
The Multidimensional Fatigue Inventory (MFI-20) is used between Visit 1 and Visits 2, 4, 5. MFI-20 is a 20-item self-administered questionnaire designed to measure fatigue in five four-item subscales: General fatigue, Physical fatigue, Reduced activity, Reduced motivation and Mental fatigue. MFI-20 has an even proportion of positively and negatively worded items that are rated on a 5-point Likert scale. Subscale scores (range 4-20) are calculated as the sum of item ratings and a total fatigue score (range 20-100) is calculated as the sum of subscale scores. Higher scores indicate a higher level of fatigue.
Time frame: Day 14 (Visit 2), Day 44±2 (Visit 4), Day 75+2 (Visit 5) compared with the baseline level (Visit 1, Day 1 of treatment)
Population: The efficacy analysis was performed for ITT-population excluding participant No. 098 whose data after the randomization visit are missing.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Main (Mexidol) | Changes in the Severity of Asthenia Assessed With the Multidimensional Fatigue Inventory (MFI-20) | MFI-20 scores at Visit 2 | 56.51 score on a scale | Standard Deviation 13.71 |
| Main (Mexidol) | Changes in the Severity of Asthenia Assessed With the Multidimensional Fatigue Inventory (MFI-20) | Difference at Visit 2 in comparison with Visit 1 | -3.26 score on a scale | Standard Deviation 9.58 |
| Main (Mexidol) | Changes in the Severity of Asthenia Assessed With the Multidimensional Fatigue Inventory (MFI-20) | MFI-20 scores at Visit 4 | 53.44 score on a scale | Standard Deviation 14.2 |
| Main (Mexidol) | Changes in the Severity of Asthenia Assessed With the Multidimensional Fatigue Inventory (MFI-20) | Difference at Visit 4 in comparison with Visit 1 | -6.37 score on a scale | Standard Deviation 11.61 |
| Main (Mexidol) | Changes in the Severity of Asthenia Assessed With the Multidimensional Fatigue Inventory (MFI-20) | MFI-20 scores at Visit 5 | 51.47 score on a scale | Standard Deviation 13.89 |
| Main (Mexidol) | Changes in the Severity of Asthenia Assessed With the Multidimensional Fatigue Inventory (MFI-20) | Difference at Visit 5 in comparison with Visit 1 | -8.33 score on a scale | Standard Deviation 12.68 |
| Control (Placebo) | Changes in the Severity of Asthenia Assessed With the Multidimensional Fatigue Inventory (MFI-20) | MFI-20 scores at Visit 5 | 54.24 score on a scale | Standard Deviation 14 |
| Control (Placebo) | Changes in the Severity of Asthenia Assessed With the Multidimensional Fatigue Inventory (MFI-20) | MFI-20 scores at Visit 2 | 57.14 score on a scale | Standard Deviation 13.79 |
| Control (Placebo) | Changes in the Severity of Asthenia Assessed With the Multidimensional Fatigue Inventory (MFI-20) | Difference at Visit 4 in comparison with Visit 1 | -3.81 score on a scale | Standard Deviation 10.15 |
| Control (Placebo) | Changes in the Severity of Asthenia Assessed With the Multidimensional Fatigue Inventory (MFI-20) | Difference at Visit 2 in comparison with Visit 1 | -1.68 score on a scale | Standard Deviation 7.24 |
| Control (Placebo) | Changes in the Severity of Asthenia Assessed With the Multidimensional Fatigue Inventory (MFI-20) | Difference at Visit 5 in comparison with Visit 1 | -4.80 score on a scale | Standard Deviation 11.42 |
| Control (Placebo) | Changes in the Severity of Asthenia Assessed With the Multidimensional Fatigue Inventory (MFI-20) | MFI-20 scores at Visit 4 | 55.23 score on a scale | Standard Deviation 14.14 |
Secondary
Changes in the Severity of Cognitive Impairment Assessed With the Montreal Cognitive Assessment Scale Between Visit 0 and Visits 2 and 4
The Montreal Cognitive Assessment (MoCA) is used to measure the changes in the severity of cognitive impairment at Visits 2 and 4 in comparison to Visit 0. MoCA scores range between 0 and 30. A score of 26 or over is considered to be normal. Higher score than shown at Visit 0 is expected.
Time frame: Day 14 (Visit 2) and Day 44±2 (Visit 4) compared with the baseline level (Visit 0, 7 days before treatment)
Population: The efficacy analysis was performed for ITT-population excluding participant No. 098 whose data after the randomization visit are missing.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Main (Mexidol) | Changes in the Severity of Cognitive Impairment Assessed With the Montreal Cognitive Assessment Scale Between Visit 0 and Visits 2 and 4 | MoCA scores at Visit 2 | 23.82 score on a scale | Standard Deviation 2.28 |
| Main (Mexidol) | Changes in the Severity of Cognitive Impairment Assessed With the Montreal Cognitive Assessment Scale Between Visit 0 and Visits 2 and 4 | Difference at Visit 2 in comparison to Visit 0 | 2.30 score on a scale | Standard Deviation 1.96 |
| Main (Mexidol) | Changes in the Severity of Cognitive Impairment Assessed With the Montreal Cognitive Assessment Scale Between Visit 0 and Visits 2 and 4 | MoCA scores at Visit 4 | 25.06 score on a scale | Standard Deviation 2.37 |
| Main (Mexidol) | Changes in the Severity of Cognitive Impairment Assessed With the Montreal Cognitive Assessment Scale Between Visit 0 and Visits 2 and 4 | Difference at Visit 4 in comparison to Visit 0 | 3.54 score on a scale | Standard Deviation 2.36 |
| Control (Placebo) | Changes in the Severity of Cognitive Impairment Assessed With the Montreal Cognitive Assessment Scale Between Visit 0 and Visits 2 and 4 | Difference at Visit 4 in comparison to Visit 0 | 1.98 score on a scale | Standard Deviation 2 |
| Control (Placebo) | Changes in the Severity of Cognitive Impairment Assessed With the Montreal Cognitive Assessment Scale Between Visit 0 and Visits 2 and 4 | MoCA scores at Visit 2 | 23.10 score on a scale | Standard Deviation 2.17 |
| Control (Placebo) | Changes in the Severity of Cognitive Impairment Assessed With the Montreal Cognitive Assessment Scale Between Visit 0 and Visits 2 and 4 | MoCA scores at Visit 4 | 23.75 score on a scale | Standard Deviation 2.34 |
| Control (Placebo) | Changes in the Severity of Cognitive Impairment Assessed With the Montreal Cognitive Assessment Scale Between Visit 0 and Visits 2 and 4 | Difference at Visit 2 in comparison to Visit 0 | 1.31 score on a scale | Standard Deviation 1.64 |
Secondary
Motor Changes Assessed With the Tinetti Test
The Tinetti test is used between Visit 1 and Visits 2, 4, 5. The Tinetti test is a clinical test for the assessment of balance and gait. It has a gait score and a balance score using a 3-point ordinal scale of 0, 1 and 2. Gait is scored over 12 and balance is scored over 16 totalling 28. The lower the score on the Tinetti test, the higher the risk of falling. Tinetti test score equal or less than 18 shows high risk of fall, 19-23 scores show moderate risk of fall, and score equal or higher than 24 shows low risk of fall. Thus, min value is 0, max value is 28, higher scores mean a better outcome.
Time frame: Day 14 (Visit 2), Day 44±2 (Visit 4), Day 75+2 (Visit 5) compared with the baseline level (Visit 1, Day 1 of treatment)
Population: The efficacy analysis was performed for ITT-population excluding participant No. 098 whose data after the randomization visit are missing.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Main (Mexidol) | Motor Changes Assessed With the Tinetti Test | Tinetti test, Visit 2 | 34.26 score on a scale | Standard Deviation 4.92 |
| Main (Mexidol) | Motor Changes Assessed With the Tinetti Test | Difference at Visit 2 in comparison with Visit 1 | 1.62 score on a scale | Standard Deviation 2.47 |
| Main (Mexidol) | Motor Changes Assessed With the Tinetti Test | Tinetti test, Visit 4 | 35.06 score on a scale | Standard Deviation 4.57 |
| Main (Mexidol) | Motor Changes Assessed With the Tinetti Test | Difference at Visit 4 in comparison with Visit 1 | 2.44 score on a scale | Standard Deviation 3.2 |
| Main (Mexidol) | Motor Changes Assessed With the Tinetti Test | Tinetti test, Visit 5 | 35.97 score on a scale | Standard Deviation 4.26 |
| Main (Mexidol) | Motor Changes Assessed With the Tinetti Test | Difference at Visit 5 in comparison with Visit 1 | 3.36 score on a scale | Standard Deviation 3.39 |
| Control (Placebo) | Motor Changes Assessed With the Tinetti Test | Tinetti test, Visit 5 | 34.75 score on a scale | Standard Deviation 4.42 |
| Control (Placebo) | Motor Changes Assessed With the Tinetti Test | Tinetti test, Visit 2 | 34.00 score on a scale | Standard Deviation 4.75 |
| Control (Placebo) | Motor Changes Assessed With the Tinetti Test | Difference at Visit 4 in comparison with Visit 1 | 1.18 score on a scale | Standard Deviation 3.51 |
| Control (Placebo) | Motor Changes Assessed With the Tinetti Test | Difference at Visit 2 in comparison with Visit 1 | 0.71 score on a scale | Standard Deviation 2.84 |
| Control (Placebo) | Motor Changes Assessed With the Tinetti Test | Difference at Visit 5 in comparison with Visit 1 | 1.55 score on a scale | Standard Deviation 4.05 |
| Control (Placebo) | Motor Changes Assessed With the Tinetti Test | Tinetti test, Visit 4 | 34.39 score on a scale | Standard Deviation 4.47 |