Ischemic Stroke, Acute
Conditions
Keywords
Ischemic Stroke, Acute Stroke, Cerebral stroke, Traumatic Brain Injury, Acute Cerebrovascular Accident, ACVA, Acute cerebral failure, Neuroprotection, Mexidol, Ethylmethylhydroxypyridine Succinate
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
Interventions
DRUGMexidol
Neurocytoprotector
Sponsors
Pharmasoft
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Acute Ischemic Stroke * Montreal Cognitive Assessment (MoCA) test \>15; ≤22
Exclusion criteria
* Under 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Аssessment of Attentiveness and Performance | Assessed before starting therapy (Day 1), at the end of the parenteral therapy phase (Day 10) and at the end of the course of therapy (Day 66). | Schulte test \[work efficiency\]. Test methodology: the subject is successively shown 5 tables (5x5), in the cells of which numbers (from 1 to 25) are randomly located. It is required to show and name all the numbers in ascending order (from 1 to 25). The time spent on each table separately is recorded. Depending on the objectives, the excess of the standard (40-50 sec) time spent on each table and the dynamics of time indicators, or the average or total result of the examination for all five tables, are analyzed \[test time: min value 30.0 sec, max value N/A; higher scores mean a worse outcome\]. |
| Dynamics of Cognitive Status | Assessed at screening (Day 0), at the end of the parenteral therapy phase (Day 10) and at the end of the course of therapy (Day 66); Day 66 reported | The Montreal Cognitive Assessment (MoCA test) \[31 point scale: min value 0, max value 30, higher scores mean a better outcome\] |
| Severity of Depression | Assessed before starting therapy (Day 1), at the end of the parenteral therapy phase (Day 10), in the middle of the oral therapy phase (Day 38) and at the end of the course of therapy (Day 66); Day 66 reported | The Beck Depression Inventory (BDI scale) \[64 point scale: min value 0, max value 63, higher scores mean a worse outcome\] |
| Reduction in Anxiety | Assessed before starting therapy (Day 1), at the end of the parenteral therapy phase (Day 10), in the middle of the oral therapy phase (Day 38) and at the end of the course of therapy (Day 66); Day 66 reported | The Hospital Anxiety and Depression Scale (HADS) \[22 point scale: min value 0, max value 21, higher scores mean a worse outcome\] |
| Severity of Post Intensive Care Syndrome | Assessed before starting therapy (Day 1), at the end of the parenteral therapy phase (Day 10), in the middle of the oral therapy phase (Day 38) and at the end of the course of therapy (Day 66); Day 66 reported | The Post Intensive Care Syndrome (PICS) score \[21 point scale: min value 0, max value 10 with 0,5 point scale division, higher scores mean a worse outcome\] |
| Dynamics of Level of Mobility | Assessed before starting therapy (Day 1), at the end of the parenteral therapy phase (Day 10), in the middle of the oral therapy phase (Day 38) and at the end of the course of therapy (Day 66); Day 66 reported | The Rivermead index \[16 point scale: min value 0, max value 15, higher scores mean a better outcome\] |
| Dynamics of the Level of Life | Assessed at screening (Day 0), at the end of the parenteral therapy phase (Day 10), in the middle of the oral therapy phase (Day 38) and at the end of the course of therapy (Day 66); Day 66 reported | The Rehabilitation Routing Scale (RRS) \[7 point scale: min value 0, max value 6, higher scores mean a worse outcome\] |
| Severity and Dynamics of Muscle Strength | Assessed before starting therapy (Day 1), at the end of the parenteral therapy phase (Day 10), in the middle of the oral therapy phase (Day 38) and at the end of the course of therapy (Day 66); Day 66 reported | The Muscle Strength Quantitative Rating (MRC) Scale \[6 point scale: min value 0, max value 5, higher scores mean a better outcome\] |
| Systolic Cerebral Blood Flow Velocity (Vs) Using Transcranial Doppler (TCD) at Key Time Points | The TCDG parameters registrated before infusion, at the start of the infusion, at the start of the Schulte test, at the end of the Schulte test, at the end of the infusion. | Systolic cerebral blood flow velocity (Vs) was measured in сm/sec using transcranial Doppler ultrasonography (TCD). Measurements were taken for each participant at five key time points: (1) before the first Mexidol infusion (Before infusion), (2) at the start of the infusion, (3) at the start of the Schulte test, (4) at the end of the Schulte test, and (5) at the end of the infusion. \[Normal values: min 35 сm/sec, max 95 сm/sec\] |
| Overshoot Coefficient (OC) of Systolic Cerebral Blood Flow Velocity (TCD) at Key Time Points | The TCDG parameters registrated before infusion, at the start of the infusion, at the start of the Schulte test, at the end of the Schulte test, at the end of the infusion. | The Overshoot Coefficient (OC) is a ratio reflecting the change in systolic cerebral blood flow velocity before and after specific stimuli. It was calculated based on transcranial Doppler measurements at five key time points: (1) before the first Mexidol infusion (Before infusion), (2) at the start of the infusion, (3) at the start of the Schulte test, (4) at the end of the Schulte test, and (5) at the end of the infusion. \[It's calculated by the formula OC=(Vo-Vs)/Vs, the norm is not less than 1.12\] |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | Throughout the study [From Day 1 up to Day 66] | Registration of adverse events related to Mexidol and significant differences in vital signs between groups |
Countries
Russia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Main (Mexidol and Standard Treatment) 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
Mexidol: Neurocytoprotector | 30 |
| Control 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 | 30 |
| Total | 60 |
Baseline characteristics
| Characteristic | Control | Main (Mexidol and Standard Treatment) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 24 Participants | 5 Participants | 29 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 25 Participants | 31 Participants |
| Age, Continuous | 66.6 years STANDARD_DEVIATION 9.4 | 63.9 years STANDARD_DEVIATION 10.3 | 65.3 years STANDARD_DEVIATION 9.8 |
| Cognitive status [MoCA] | 19.6 units on a scale STANDARD_DEVIATION 1.83 | 19.1 units on a scale STANDARD_DEVIATION 2.26 | 19.35 units on a scale STANDARD_DEVIATION 2.05 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Region of Enrollment Russia | 30 participants | 30 participants | 60 participants |
| Sex: Female, Male Female | 17 Participants | 13 Participants | 30 Participants |
| Sex: Female, Male Male | 13 Participants | 17 Participants | 30 Participants |
| The Rehabilitation Routing Scale (RRS) | 4.1 units on a scale STANDARD_DEVIATION 0.5 | 3.9 units on a scale STANDARD_DEVIATION 0.4 | 4.0 units on a scale STANDARD_DEVIATION 0.5 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 30 | 0 / 30 |
| other Total, other adverse events | 0 / 30 | 0 / 30 |
| serious Total, serious adverse events | 0 / 30 | 0 / 30 |
Outcome results
Primary
Dynamics of Cognitive Status
The Montreal Cognitive Assessment (MoCA test) \[31 point scale: min value 0, max value 30, higher scores mean a better outcome\]
Time frame: Assessed at screening (Day 0), at the end of the parenteral therapy phase (Day 10) and at the end of the course of therapy (Day 66); Day 66 reported
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Main (Mexidol and Standard Treatment) | Dynamics of Cognitive Status | 23.8 score on a scale | Standard Deviation 2.6 |
| Control | Dynamics of Cognitive Status | 22.9 score on a scale | Standard Deviation 3 |
Primary
Dynamics of Level of Mobility
The Rivermead index \[16 point scale: min value 0, max value 15, higher scores mean a better outcome\]
Time frame: Assessed before starting therapy (Day 1), at the end of the parenteral therapy phase (Day 10), in the middle of the oral therapy phase (Day 38) and at the end of the course of therapy (Day 66); Day 66 reported
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Main (Mexidol and Standard Treatment) | Dynamics of Level of Mobility | 10.3 score on a scale | Standard Deviation 2.8 |
| Control | Dynamics of Level of Mobility | 8.0 score on a scale | Standard Deviation 2.8 |
Primary
Dynamics of the Level of Life
The Rehabilitation Routing Scale (RRS) \[7 point scale: min value 0, max value 6, higher scores mean a worse outcome\]
Time frame: Assessed at screening (Day 0), at the end of the parenteral therapy phase (Day 10), in the middle of the oral therapy phase (Day 38) and at the end of the course of therapy (Day 66); Day 66 reported
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Main (Mexidol and Standard Treatment) | Dynamics of the Level of Life | 2.9 score on a scale | Standard Deviation 0.7 |
| Control | Dynamics of the Level of Life | 3.3 score on a scale | Standard Deviation 0.6 |
Primary
Overshoot Coefficient (OC) of Systolic Cerebral Blood Flow Velocity (TCD) at Key Time Points
The Overshoot Coefficient (OC) is a ratio reflecting the change in systolic cerebral blood flow velocity before and after specific stimuli. It was calculated based on transcranial Doppler measurements at five key time points: (1) before the first Mexidol infusion (Before infusion), (2) at the start of the infusion, (3) at the start of the Schulte test, (4) at the end of the Schulte test, and (5) at the end of the infusion. \[It's calculated by the formula OC=(Vo-Vs)/Vs, the norm is not less than 1.12\]
Time frame: The TCDG parameters registrated before infusion, at the start of the infusion, at the start of the Schulte test, at the end of the Schulte test, at the end of the infusion.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Main (Mexidol and Standard Treatment) | Overshoot Coefficient (OC) of Systolic Cerebral Blood Flow Velocity (TCD) at Key Time Points | Before infusion | 1.25 ratio | Standard Deviation 0.05 |
| Main (Mexidol and Standard Treatment) | Overshoot Coefficient (OC) of Systolic Cerebral Blood Flow Velocity (TCD) at Key Time Points | Start of the infusion | 1.26 ratio | Standard Deviation 0.04 |
| Main (Mexidol and Standard Treatment) | Overshoot Coefficient (OC) of Systolic Cerebral Blood Flow Velocity (TCD) at Key Time Points | Start of the Schulte test | 1.25 ratio | Standard Deviation 0.05 |
| Main (Mexidol and Standard Treatment) | Overshoot Coefficient (OC) of Systolic Cerebral Blood Flow Velocity (TCD) at Key Time Points | End of the Schulte test | 1.26 ratio | Standard Deviation 0.05 |
| Main (Mexidol and Standard Treatment) | Overshoot Coefficient (OC) of Systolic Cerebral Blood Flow Velocity (TCD) at Key Time Points | End of the infusion | 1.27 ratio | Standard Deviation 0.05 |
| Control | Overshoot Coefficient (OC) of Systolic Cerebral Blood Flow Velocity (TCD) at Key Time Points | End of the infusion | 1.28 ratio | Standard Deviation 0.04 |
| Control | Overshoot Coefficient (OC) of Systolic Cerebral Blood Flow Velocity (TCD) at Key Time Points | End of the Schulte test | 1.27 ratio | Standard Deviation 0.04 |
| Control | Overshoot Coefficient (OC) of Systolic Cerebral Blood Flow Velocity (TCD) at Key Time Points | Start of the infusion | 1.27 ratio | Standard Deviation 0.04 |
| Control | Overshoot Coefficient (OC) of Systolic Cerebral Blood Flow Velocity (TCD) at Key Time Points | Before infusion | 1.27 ratio | Standard Deviation 0.05 |
| Control | Overshoot Coefficient (OC) of Systolic Cerebral Blood Flow Velocity (TCD) at Key Time Points | Start of the Schulte test | 1.27 ratio | Standard Deviation 0.04 |
Primary
Reduction in Anxiety
The Hospital Anxiety and Depression Scale (HADS) \[22 point scale: min value 0, max value 21, higher scores mean a worse outcome\]
Time frame: Assessed before starting therapy (Day 1), at the end of the parenteral therapy phase (Day 10), in the middle of the oral therapy phase (Day 38) and at the end of the course of therapy (Day 66); Day 66 reported
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Main (Mexidol and Standard Treatment) | Reduction in Anxiety | 2.6 score on a scale | Standard Deviation 2.4 |
| Control | Reduction in Anxiety | 4.4 score on a scale | Standard Deviation 2.4 |
Primary
Severity and Dynamics of Muscle Strength
The Muscle Strength Quantitative Rating (MRC) Scale \[6 point scale: min value 0, max value 5, higher scores mean a better outcome\]
Time frame: Assessed before starting therapy (Day 1), at the end of the parenteral therapy phase (Day 10), in the middle of the oral therapy phase (Day 38) and at the end of the course of therapy (Day 66); Day 66 reported
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Main (Mexidol and Standard Treatment) | Severity and Dynamics of Muscle Strength | 3.3 score on a scale | Standard Deviation 5.1 |
| Control | Severity and Dynamics of Muscle Strength | 2.1 score on a scale | Standard Deviation 2.2 |
Primary
Severity of Depression
The Beck Depression Inventory (BDI scale) \[64 point scale: min value 0, max value 63, higher scores mean a worse outcome\]
Time frame: Assessed before starting therapy (Day 1), at the end of the parenteral therapy phase (Day 10), in the middle of the oral therapy phase (Day 38) and at the end of the course of therapy (Day 66); Day 66 reported
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Main (Mexidol and Standard Treatment) | Severity of Depression | 7.5 score on a scale | Standard Deviation 4.5 |
| Control | Severity of Depression | 11.4 score on a scale | Standard Deviation 5.6 |
Primary
Severity of Post Intensive Care Syndrome
The Post Intensive Care Syndrome (PICS) score \[21 point scale: min value 0, max value 10 with 0,5 point scale division, higher scores mean a worse outcome\]
Time frame: Assessed before starting therapy (Day 1), at the end of the parenteral therapy phase (Day 10), in the middle of the oral therapy phase (Day 38) and at the end of the course of therapy (Day 66); Day 66 reported
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Main (Mexidol and Standard Treatment) | Severity of Post Intensive Care Syndrome | 0.02 score on a scale | Standard Deviation 0.09 |
| Control | Severity of Post Intensive Care Syndrome | 0.3 score on a scale | Standard Deviation 0.6 |
Primary
Systolic Cerebral Blood Flow Velocity (Vs) Using Transcranial Doppler (TCD) at Key Time Points
Systolic cerebral blood flow velocity (Vs) was measured in сm/sec using transcranial Doppler ultrasonography (TCD). Measurements were taken for each participant at five key time points: (1) before the first Mexidol infusion (Before infusion), (2) at the start of the infusion, (3) at the start of the Schulte test, (4) at the end of the Schulte test, and (5) at the end of the infusion. \[Normal values: min 35 сm/sec, max 95 сm/sec\]
Time frame: The TCDG parameters registrated before infusion, at the start of the infusion, at the start of the Schulte test, at the end of the Schulte test, at the end of the infusion.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Main (Mexidol and Standard Treatment) | Systolic Cerebral Blood Flow Velocity (Vs) Using Transcranial Doppler (TCD) at Key Time Points | Start of the Schulte test | 74.6 сm/sec | Standard Deviation 18.73 |
| Main (Mexidol and Standard Treatment) | Systolic Cerebral Blood Flow Velocity (Vs) Using Transcranial Doppler (TCD) at Key Time Points | Before infusion | 72.6 сm/sec | Standard Deviation 18.41 |
| Main (Mexidol and Standard Treatment) | Systolic Cerebral Blood Flow Velocity (Vs) Using Transcranial Doppler (TCD) at Key Time Points | End of the infusion | 78.53 сm/sec | Standard Deviation 17.78 |
| Main (Mexidol and Standard Treatment) | Systolic Cerebral Blood Flow Velocity (Vs) Using Transcranial Doppler (TCD) at Key Time Points | Start of the infusion | 72.23 сm/sec | Standard Deviation 17.68 |
| Main (Mexidol and Standard Treatment) | Systolic Cerebral Blood Flow Velocity (Vs) Using Transcranial Doppler (TCD) at Key Time Points | End of the Schulte test | 76.83 сm/sec | Standard Deviation 17.76 |
| Control | Systolic Cerebral Blood Flow Velocity (Vs) Using Transcranial Doppler (TCD) at Key Time Points | End of the infusion | 83.57 сm/sec | Standard Deviation 32.29 |
| Control | Systolic Cerebral Blood Flow Velocity (Vs) Using Transcranial Doppler (TCD) at Key Time Points | Start of the Schulte test | 83.57 сm/sec | Standard Deviation 34.3 |
| Control | Systolic Cerebral Blood Flow Velocity (Vs) Using Transcranial Doppler (TCD) at Key Time Points | End of the Schulte test | 80.87 сm/sec | Standard Deviation 31.98 |
| Control | Systolic Cerebral Blood Flow Velocity (Vs) Using Transcranial Doppler (TCD) at Key Time Points | Start of the infusion | 80.8 сm/sec | Standard Deviation 33.09 |
| Control | Systolic Cerebral Blood Flow Velocity (Vs) Using Transcranial Doppler (TCD) at Key Time Points | Before infusion | 80.03 сm/sec | Standard Deviation 33.49 |
Primary
Аssessment of Attentiveness and Performance
Schulte test \[work efficiency\]. Test methodology: the subject is successively shown 5 tables (5x5), in the cells of which numbers (from 1 to 25) are randomly located. It is required to show and name all the numbers in ascending order (from 1 to 25). The time spent on each table separately is recorded. Depending on the objectives, the excess of the standard (40-50 sec) time spent on each table and the dynamics of time indicators, or the average or total result of the examination for all five tables, are analyzed \[test time: min value 30.0 sec, max value N/A; higher scores mean a worse outcome\].
Time frame: Assessed before starting therapy (Day 1), at the end of the parenteral therapy phase (Day 10) and at the end of the course of therapy (Day 66).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Main (Mexidol and Standard Treatment) | Аssessment of Attentiveness and Performance | Day 1 | 94.9 seconds |
| Main (Mexidol and Standard Treatment) | Аssessment of Attentiveness and Performance | Day 10 | 75 seconds |
| Main (Mexidol and Standard Treatment) | Аssessment of Attentiveness and Performance | Day 66 | 71.7 seconds |
| Control | Аssessment of Attentiveness and Performance | Day 1 | 71.2 seconds |
| Control | Аssessment of Attentiveness and Performance | Day 10 | 68.15 seconds |
| Control | Аssessment of Attentiveness and Performance | Day 66 | 63 seconds |
Secondary
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Registration of adverse events related to Mexidol and significant differences in vital signs between groups
Time frame: Throughout the study [From Day 1 up to Day 66]
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Main (Mexidol and Standard Treatment) | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | 0 Adverse events |
| Control | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | 0 Adverse events |