Clinical trial NCT06221826
Conditions: Ischemic Stroke, Acute
Keywords: Ischemic Stroke Acute Stroke Cerebral stroke Traumatic Brain Injury Acute Cerebrovascular Accident ACVA Acute cerebral failure Neuroprotection Mexidol Ethylmethylhydroxypyridine Succinate
Sponsor: Pharmasoft
Start date: 2023-04-17; Completion date: 2023-09-12
Enrollment: 60 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The use of metabolic modulators creates prospects for increasing the efficiency of the rehabilitation treatment of patients with acute cerebral failure

Detailed description:
Modern neurorehabilitation is a set of basic and adjuvant treatment methods that provide a modulating effect on the neurorestoration process. The range of basic rehabilitation practices includes kinesiotherapy, occupational therapy, speech therapy, and neuropsychology. Adjuvant methods include physiotherapeutic and medicinal methods. For this study, the investigators chose MEXIDOL® as an adjuvant metabolic medicine, which has the ability to modulate receptor complexes of brain membranes, in particular benzodiazepine, GABA, acetylcholine, enhancing their ability to bind to specific ligands. This pharmacodynamic feature of the drug can have a positive effect on the psycho-emotional state of patients, which in turn will increase motivation and, consequently, the success of the rehabilitation process

Arms: arm 1: Mexidol IV 500 mg for 10 days, then Mexidol FORTE 250 orally 250 mg 1 tablet 3 times a day for 8 weeks; and standard treatment arm 2: Standard treatment: basic practices of kinesitherapy, occupational therapy, speech therapy, clinical psychology, supplemented by adjuvant procedures of electrotherapy and rehabilitation environment therapy. The patient's rehabilitation load was at least 3 hours a day for 12 days
Interventions: intervention 1: Mexidol
Intervention descriptions: intervention 1: Neurocytoprotector

Protocol documents:
Prot_SAP_000.pdf: 
Page 1 / 6 
 
 
 
 
 
Study Protocol with Statistical Analysis Plan 
 
 
 
 
Prospective Randomized Study of the modulating effect of MEXIDOL® 
as an adjuvant stimulant of the cognitive-emotional component of the 
rehabilitation treatment in patients with acute cerebral failure 
 
 
NCT Number: NCT06221826 
 
 
 
 
 
 
 
 
 
Pharmasoft 
April 10, 2023 
 


Page 2 / 6 
Study Protocol 
The study procedures for the visits are presented in Table 1. 
Conditions 
Acute Cerebral Failure (Ischemic Stroke, Traumatic Brain Injury) 
Study Design 
Study Type: Interventional 
Primary Purpose: Treatment 
Study Phase: Phase 4 
Interventional Study Model: Parallel Assignment 
Number of Arms: 2 
Masking: None (Open Label) 
Allocation: Randomized (1:1) 
Enrollment: 60 [Actual] 
Time Frame: 66 days (I: parenteral therapy 10 days; II: oral therapy 8 
weeks) 
Arms 
1. Mexidol and Standard Therapy 
2. Standard Therapy  
Method of Application 
Mexidol, 
solution 
for 
intravenous 
(IV) 
and 
intramuscular 
administration, IV 500 mg for 10 days, then Mexidol FORTE 250, film-
coated tablets 250 mg, orally 1 tablet 3 times a day for 8 weeks. 
Standard and 
Concomitant therapy 
Standard treatment: basic practices of kinesitherapy, occupational 
therapy, speech therapy, clinical psychology, supplemented by adjuvant 
procedures of electrotherapy and rehabilitation environment therapy. 
The patient's rehabilitation load was at least 3 hours a day for 12 days. 
Patients may continue their pre-study therapy for other chronic 
conditions if, in the opinion of the investigator, they do not interfere 
with the results of this study and are administered at a stable dose during 
the study. 
Primary Purpose 
To evaluate the effect of pharmacological modulation of the 
rehabilitation process with the drug Mexidol as an adjuvant component 
of rehabilitation treatment of emotional and cognitive disorders in 
patients with Acute Cerebral Failure (Ischemic Stroke, Traumatic Brain 
Injury). 
Secondary Purpose 
To establish the possibility of identifying an individual clinical response 
to Mexidol therapy (responders and non-responders) and to determine 
indications for including the drug in an individual rehabilitation 
program. 
Exploratory Purpose 
 
To establish, using neurophysiological methods, the effect of the 
drug on perfusion-metabolic coupling (TCDG-EEG [transcranial 
dopplerography and electroencephalography] monitoring at the time 
of drug infusion) as an indirect indicator of increased metabolic 
activity of the brain. 
 To establish, using clinical scales, the presence of a connection 
between the use of the drug Mexidol and the dynamics of recovery 
of the emotional-cognitive status of patients with acute cerebral 
insufficiency, during the period of permanent inpatient-outpatient 
rehabilitation treatment. 
Research objectives 
(Outcome Measures) 
1. Аssessment of attentiveness and performance – the presence of the 
effect of Mexidol infusion on the change in the results of the Schulte 
test [work efficiency] before the start of the course, at the end of the 


Page 3 / 6 
course of infusion therapy and after the course of therapy with the 
tablet form of Mexidol FORTE 250 
2. Dynamics of cognitive status according to the Montreal Cognitive 
Assessment (MoCA test) 
3. Severity of depression according to the Beck Depression Inventory 
(BDI scale) 
4. Reduction in anxiety according to the Hospital Anxiety and 
Depression Scale (HADS) 
5. The degree of severity and dynamics of the Post Intensive Care 
Syndrome (PICS) according to the PICS-score  
6. Dynamics of level of mobility according to the Rivermead index 
7. Dynamics of the level of life according to the Rehabilitation Routing 
Scale (RRS) 
8. Severity and dynamics of muscle strength according to the Muscle 
Strength Quantitative Rating (MRC) Scale  
9. Variants of specific dynamics of neurophysiological parameters of 
perfusion 
(transcranial 
dopplerography) 
and 
metabolism 
(electroencephalography) at the time of infusion of Mexidol (event 
related monitoring) 
Safety and Tolerability 
Criteria: 
Incidence of Treatment-Emergent Adverse events related to Mexidol 
Inclusion Criteria: 
• 
≥18 years old 
• 
Signed Informed Consent Form 
• 
Acute Cerebral Failure (Ischemic Stroke, Traumatic Brain Injury) 
• 
Montreal Cognitive Assessment (MoCA test) >15; ≤22 
Exclusion Criteria: 
• 
 18 years old 
• 
Epilepsy 
• 
Pregnancy 
• 
Acute failure of one or more organ systems 
• 
Purulent-inflammatory disease of any localization 
• 
Participating in any other clinical trial 
Ethical and Legal Aspects 
This study will be conducted with the highest respect for the individual 
participants in accordance with the requirements of this study protocol 
and also in accordance with the following: 
• 
The ethical principles that have their origin in the Declaration of 
Helsinki. 
• 
International Conference on Harmonisation E6 Good Clinical 
Practice: Consolidated Guideline. 
• 
All applicable laws and regulations, including, without limitation, 
privacy laws, clinical trial disclosure laws, and regulations. 


Page 4 / 6 
Table 1. Schedule of study procedures. 
 
The study procedures 
Visit 
Screening 
 
Visit 1 
Day -5/-1 
Visit 2 
Day 1 
Visit 3 
Day 10  
Video 
visit 4 
Day 38 
Visit 5 
Day 66  
Obtaining Informed Consent 
X 
 
 
 
 
Checking inclusion/exclusion criteria 
X 
X 
 
 
 
Collection of anamnesis data 
X 
 
 
 
 
Conducting a physical examination 
X 
X 
 
 
 
Measurement of BMI 
X 
 
 
 
 
Body temperature 
X 
 
 
 
 
Vital signs of the body's condition (mean BP, HR, RR) 
X 
X 
X 
 
X 
Randomization 
 
Х 
 
 
 
The Rehabilitation Routing Scale (RRS) 
X 
 
X 
X 
X 
The Montreal Cognitive Assessment (MoCA test) 
X 
 
X 
 
X 
The Beck Depression Inventory (BDI scale) 
 
X 
X 
X 
X 
The Hospital Anxiety and Depression Scale (HADS) 
 
X 
X 
X 
X 
The Rivermead index 
 
X 
X 
X 
X 
The Muscle Strength Quantitative Rating Scale (MRC) 
 
X 
X 
X 
X 
The Post Intensive Care Syndrome (PICS) score 
 
X 
X 
X 
X 
The Schulte test 
 
Х 
Х 
 
Х 
Neurophysiological parameters (EEG, TCDG) 
 
Х 
 
 
 
Administration of the study drug intravenously 
 
       X-------------X 
 
 
Dispensation of the study drug for oral administration 
 
 
Х 
 
 
Return of the drug and assessment of treatment compliance (if the drug is taken orally) 
 
 
 
 
X 
Question about the intake of concomitant drugs 
X 
X 
Х 
Х 
X 
Monitoring of adverse events 
 
X 
Х 
Х 
X 
 


Page 5 / 6 
Statistical Analysis Plan 
To create conditions for an independent assessment of the obtained results, statistical data 
processing at the end of the study will be performed by employees not involved in the management of 
patients participating in the study. Data processing will be performed in the software environment of the 
TIBCO® Statistica™ v.13 and R v.4.4.1 and higher packages or similar, corresponding to the tasks of 
statistical analysis.  
For statistical analysis of quantitative features, compliance with the normal distribution law will 
be preliminarily assessed by one of the generally accepted methods (Shapiro-Wilk criterion). When 
testing statistical hypotheses for indicators with a normal distribution, parametric criteria will be used, 
and for indicators whose distribution differs from normal, nonparametric criteria will be used. 
The following indicators will be calculated as descriptive statistics parameters for continuous 
(quantitative) data: 
• n – number of valid observations; 
• M, Mean – arithmetic mean; 
• Me, Median – median; 
• Min – minimum value; 
• Max – maximum value; 
• Q1 – lower quartile; 
• Q3 – upper quartile; 
• Range – range; 
• IQR – interquartile range; 
• SD – standard deviation; 
• SE – standard error of the mean; 
• w – Wilcoxon-Mann-Whitney test for independent groups; 
• t – Student's t-test with Welch's correction for independent groups; 
• f – Fisher's exact test; 
• χ2 – Chi-square test. 
For ordinal, categorical and qualitative variables: 
• absolute frequency (number of observations); 
• relative frequency (expressed as a percentage). 
The results of the assessment of quantitative variables, the distribution of which corresponds to the 
law of normal distribution, will be presented as M±SD, where M is the mean value, and SD is the 
standard deviation. The results of the assessment of quantitative variables, the distribution of which does 
not correspond to the law of normal distribution, will be presented as Me [Q1; Q3], where Me is the 
median, and Q1 and Q3 are the lower and upper quartiles. 
Efficacy and safety indicators, as well as their changes, will be presented using descriptive 
statistics by visits and therapeutic groups. For study visits, qualitative (dichotomous) indicators will be 
compared between groups based on the Pearson χ2 criterion, the Pearson χ2 criterion with Welch's 
correction, or the Fisher exact test for tables of arbitrary dimension (if the frequency of the indicator in 
at least one of the subgroups is 5 or less). 
Comparison of groups by quantitative indicators can be carried out using the Student's T-test and 
the Mann-Whitney test. Comparison of intra-group parameters before and after treatment can be 


Page 6 / 6 
performed using the T-test for related samples or the Wilcoxon-Mann-Whitney test. Statistically 
significant values are p-level <0.05. 
Safety analysis will be performed for the safety population. The following safety parameters are 
provided for in this study: 
• Total number of AEs, stratified by severity and frequency; 
• Frequency of AEs, related, in the opinion of the physician-investigator, to the use of the study 
drug; 
• Frequency of serious adverse events (SAEs), related, in the opinion of the physician-investigator, 
to the use of the study drug; 
• Proportion of patients with at least one AE; 
• Proportion of patients with 2 or more AEs. 
The dynamics of quantitative safety parameters relative to baseline values will be assessed and 
compared with each other using ANOVA with repeated measures. This method allows to simultaneously 
check for statistically significant dynamics (at least one average value at one time point differs from the 
others), and also to compare the dynamics and ranges of the indicator values when obtaining the 
compared drugs. In case of inappropriateness of the use of parametric methods, a similar analysis of the 
change in the distribution of indicators during therapy will be carried out using non-parametric analogues 
- the Friedman criterion and the Wilcoxon signed rank criterion, and intergroup comparisons of changes 
- using the Wilcoxon-Mann-Whitney criterion.