The clinical trial to valuate efficacy and safety of MMH-MAP in the treatment of cognitive disorders in patients with ischemic stroke in the carotid arteries.
Design: double-blind, randomized, parallel group placebo-controlled clinical study of efficacy and safety of MMH-MAP in the treatment of cognitive disorders in patients with ischemic stroke in the carotid arteries. The study will enroll hospitalized subjects of either gender aged 40-75 years old with verified diagnosis of ischemic stroke in the carotid arteries within 72 hours post debut having moderate cognitive disorders, moderate neurological deficit. At Visit 1 (day 1) the subject's complaints and medical history will be collected, objective examination, safety laboratory tests (hematology, serum chemistry, urinalysis) will be performed. The investigator will evaluate the patient's level of consciousness using The Glasgow Coma Scale, intensity of cognitive disorders using The Montreal Cognitive Assessment (МоСА), condition using National Institute of Health Stroke Scale (NIHSS) and The Modified Rankin Scale (mRs). Concomitant therapy will be recorded and changes in cerebral CT/MRI will be evaluated. If the subject meets inclusion criteria and has no exclusion criteria, he/she will be randomized to MMH-MAP or Placebo group. The first dose of the study product should be taken within 72 hours post stroke debut. At Visit 2 (day 12±3, end of hospitalization period - the last day of hospitalization due to the current stroke) complaints will be collected, objective examination findings will be recorded, monitoring of the prescribed and concomitant therapy will be performed, treatment safety, compliance and stroke severity according to NIHSS will be evaluated. By the end of hospital therapy the subject will be switched to outpatient therapy with continuation of IMP and medical assistance designed for the treatment of stroke and its sequelae. At Visit 3 (day 45±7 days) the investigator will make a phone call to the subject evaluating the treatment safety. At final Visit 4 (day 90±7 days) complaints will be collected, objective examination findings will be recorded, monitoring of the prescribed and concomitant therapy will be performed, treatment safety, compliance, condition according to NIHSS will be evaluated, mRs, Clinical Global Impression Efficacy Index (CGI-EI) will be filled. The investigator will perform MoCA testing. Safety laboratory tests (hematology, serum chemistry, urinalysis) will be carried out. Throughout the study the patient will receive the treatment approved by the decree of the RF Ministry of Health dated 29.12.2012 No. 740n "On approval of standard of special care in cerebral infarction" except for the products specified in section "Forbidden concomitant therapy".
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
246
The First City Clinical Hospital named after E.E. Volosevich
Average MoCA Score.
Montreal Cognitive Assessment Scale (The Montreal Cognitive Assessment, MoCA) will be used to identify moderate cognitive impairment, as well as to assess changes in cognitive functions during therapy. The maximum possible number of points is 30; 26 points or more is considered normal. The minimum score is 0, higher score is better.
Time frame: On baseline and on 90th day of the treatment.
Changes in NIHSS Score.
NIHSS Scale (National Institutes of Health Stroke Scale) is a scale for assessing the severity of neurological disorders of the acute period of ischemic stroke. The NIHSS scale involves the assessment of a neurological condition by generally accepted methods of clinical examination of reflexes, sensory organs, and the patient's level of consciousness. The results range from minimum indicators - normal or close to normal, to maximum - reflect the degree of neurological damage. The score varies between 0 and 42, lower score is better.
Time frame: On baseline, on 12th and on 90th days of the treatment.
Percentage of Patients With no Significant Disabilities.
The modified Rankin scale (mRs 0-1) allows to assess the grade of disability after a stroke. The scale includes five grades of disability: from 0 to 5: 0 - no symptoms, 5 - gross disability; bedridden, fecal and urinary incontinence, need for constant assistance by medical staff.
Time frame: On 90th day of the treatment.
Therapeutic and Side Effects, Efficacy Index.
According to Clinical Global Impression Efficacy Index (CGI-EI).CGI-EI is filled out by an investigator. It is necessary to indicate the level of efficacy of the therapy and the grade of safety of the therapy and circle the index values at the intersection of the selected lines. Evaluation of the response to treatment should take into account both therapeutic efficacy and treatment-related side effects. Side effects score varies from 1 to 4 (lower is better). Therapeutic effect score varies from 1 to 4 (higher is better). The efficacy index is "Therapeutic effect score" divided by "Side effects score", so efficacy index varies from 0.25 to 4 (higher is better).
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Arkhangelsk, Russia
Arkhangelsk Regional Clinical Hospital/Neurological Department
Arkhangelsk, Russia
Belgorod Regional Clinical Hospital of St. Joasaph
Belgorod, Russia
Regional Clinical Hospital # 3
Chelyabinsk, Russia
Kazan State Medical University/Republican Clinical Hospital of the Ministry of Health of the Republic of Tatarstan
Kazan', Russia
Interregional Clinical Diagnostic Center
Kazan', Russia
City Clinical Hospital # 7
Kazan', Russia
Research Institute - Regional Clinical Hospital # 1 named after Prof. S.V. Ochapovsky
Krasnodar, Russia
City Clinical Hospital named after V.M. Buyanov, Moscow Department of Health
Moscow, Russia
Central Clinical Hospital of the Russian Academy of Sciences
Moscow, Russia
...and 12 more locations
Time frame: On 90th day of the treatment period.
Presence of Adverse Events (AEs).
Based on medical records. Outcome measure represents the amount of participants having at least one adverse event on record.
Time frame: For 90 days of the treatment period.
Percentage of Patients With Complication of Cerebral Infarction.
Based on medical records. The sequelae of cerebral infarction (severe infections - hospital-acquired pneumonia, uroinfection; deep venous thrombosis, PATE; epileptic episodes).
Time frame: For 90 days of the treatment period.
Death Rate.
Based on medical records. Frequency of all-cause mortality outcomes.
Time frame: For 90 days of the treatment period.
Changes in Vital Signs (Pulse Rate (Heart Rate)).
Based on medical records. Vital signs will be measured in a medical setting.
Time frame: Visit 1 (day 1), Visit 2 (day 12), and Visit 4 (day 90).
Changes in Vital Signs (Respiration Rate (Breathing Rate)).
Based on medical records. Vital signs will be measured in a medical setting.
Time frame: Visit 1 (day 1), Visit 2 (day 12), and Visit 4 (day 90)
Changes in Vital Signs (Blood Pressure).
Based on medical records. Vital signs are measured in a medical setting. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) are presented.
Time frame: Visit 1 (day 1), Visit 2 (day 12), and Visit 4 (day 90).
Percentage of Patients With Clinically Significant Abnormal Laboratory Data.
Based on medical records. Laboratory tests include the following parameters (absolute and relative values): hematology, biochemistry and urinalysis. Laboratory tests will be made by central laboratory. Hemoglobin: less than or equal to (\<=) 115 grams per liter (g/L); greater than or equal to (\>=)185 g/L; decreased from baseline (DFB) \>=20 g/L Hematocrit: \<=0.37 volume/volume (v/v); \>=0.55 v/v Erythrocytes: \>=6 Tera/L Leukocytes: \>=16.0 Giga/L Neutrophils: \<1.0 Giga/L (B); Lymphocytes: greater than (\>) 4.0 Giga/L Monocytes: \>0.7 Giga/L Basophils: \>0.1 Giga/L Eosinophils: \>0.5 Giga/L or \>upper limit of normal (ULN) (if ULN \>=0.5 Giga/L) Sodium: \<=129 millimoles (mmol)/L; \>=160 mmol/L Potassium: \<3 mmol/L; \>=5.5 mmol/L Alanine Aminotransferase (ALT): \>3 ULN Aspartate aminotransferase (AST): \>3 ULN Alkaline phosphatase: \>1.5 ULN Bilirubin: \>1.5 ULN Creatinine: \>=150 micromoles per liter (mcmol/L); \>=30% change from baseline.
Time frame: On baseline and on 90th day of the treatment.
Percentage of Patients With Recurring Cerebral Infarction.
The percentage of patients with recurrent cerebral infarction for 90 days of the treatment period is estimated from medical records.
Time frame: For 90 days of the treatment period.