Clinical trial NCT04295681: Clinical Trial of Efficacy and Safety of MMH-MAP in the Treatment of Cognitive Disorders
Official title: A Multicenter, Double-blind, Randomized, Parallel Group Placebo-controlled Clinical Trial of Efficacy and Safety of MMH-MAP in the Treatment of Cognitive Disorders in Patients With Ischemic Stroke in the Carotid Arteries
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cognitive Disorders
Lead sponsor: Materia Medica Holding
Sponsor class: INDUSTRY
First posted: 2020-03-04
Enrollment: 246
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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".

Eligibility criteria: Inclusion Criteria:

1. Age between 40 and 75 years old inclusively.
2. Ischemic stroke in the carotid arteries (I 63) within 72 hours post debut.
3. Moderate cognitive disorders (MoCA \< 26).
4. Normal consciousness (Glasgow score 15)
5. Stroke severity 8-12 according to NIHSS.
6. Disability mRs score 2-3.
7. Availability of cerebral CT/MRI within 72 hours post stroke debut.
8. Patients who agreed to use a reliable method of contraception during the study.
9. Patients who have signed the Participant Information Sheet and Informed Consent.

Exclusion Criteria:

1. Current or previous subarachnoidal/parenchymatous/ventricular hemorrhage, cerebral infarction, cerebral tumour.
2. Cerebral CT/MRI findings suggesting cerebral hemorrhage, tumour within 72 hours post stroke debut.
3. Scheduled or completed thrombolytic therapy for the treatment of the current cerebral infarction.
4. Central nervous system (CNS) diseases including:

   * Inflammatory diseases of the central nervous system (G00-G09);
   * Systemic atrophies primarily affecting the central nervous system (G10-G13);
   * Extrapyramidal and movement disorders (G20-G26);
   * Other degenerative diseases of the nervous system (G30-G32);
   * Demyelinating diseases of the CNS (G35-G37);
   * Episodic and paroxysmal disorders (G40-G47);
   * Polyneuropathies and other disorders of the peripheral nervous system (G60-64), with marked movement and/or sensory impairments that cause movement disorders;
   * Hydrocephalus (G91).
5. Head injuries (S00-S09) (including history), accompanied by impaired consciousness, brain contusion or open craniocerebral injuries.
6. Musculoskeletal disorders causing motor disturbances.
7. Dementia (including history) (F00-F03).
8. Malignant neoplasms.
9. Patients previously diagnosed with class IV heart failure (1964 New York Heart Association functional classification), hypothyroidism, or poorly treated diabetes mellitus.
10. Patients having unstable angina or myocardial infarction in the past 6 months.
11. Allergy/ intolerance to any of the components of medications used in the treatment.
12. Malabsorption syndrome, including congenital or acquired lactase deficiency (or any other disaccharidase deficiency) and galactosemia.
13. Any conditions which, according to the investigator opinion, may interfere with the subject's participation in the study.
14. Prior history of non-adherence to a drug regimen, a psychiatric disorder, alcoholism or drug abuse, which, in the opinion of the investigator, can compromise compliance with study protocol.
15. Pregnancy, breast-feeding; childbirth less than 3 months prior to the inclusion in the trial, unwillingness to use contraceptive methods during the trial.
16. Participation in other clinical studies within 3 month prior to enrollment in the study.
17. Patients who are related to any of the on-site research personnel directly involved in the conduct of the trial or are an immediate relative of the study investigator. 'Immediate relative' means husband, wife, parent, son, daughter, brother, or sister (regardless of whether they are natural or adopted).
18. Patients who work for OOO "NPF "Materia Medica Holding" (i.e. the company's employees, temporary contract workers, designated officials responsible for carrying out the research or any immediate relatives of the aforementioned).

Primary outcomes:
measure: Average MoCA Score.
timeFrame: On baseline and on 90th day of the treatment.
Secondary outcomes:
measure: Changes in NIHSS Score.
timeFrame: On baseline, on 12th and on 90th days of the treatment.
measure: Percentage of Patients With no Significant Disabilities.
timeFrame: On 90th day of the treatment.
measure: Therapeutic and Side Effects, Efficacy Index.
timeFrame: On 90th day of the treatment period.
measure: Presence of Adverse Events (AEs).
timeFrame: For 90 days of the treatment period.
measure: Percentage of Patients With Complication of Cerebral Infarction.
timeFrame: For 90 days of the treatment period.
measure: Death Rate.
timeFrame: For 90 days of the treatment period.
measure: Changes in Vital Signs (Pulse Rate (Heart Rate)).
timeFrame: Visit 1 (day 1), Visit 2 (day 12), and Visit 4 (day 90).
measure: Changes in Vital Signs (Respiration Rate (Breathing Rate)).
timeFrame: Visit 1 (day 1), Visit 2 (day 12), and Visit 4 (day 90)
measure: Changes in Vital Signs (Blood Pressure).
timeFrame: Visit 1 (day 1), Visit 2 (day 12), and Visit 4 (day 90).
measure: Percentage of Patients With Clinically Significant Abnormal Laboratory Data.
timeFrame: On baseline and on 90th day of the treatment.
measure: Percentage of Patients With Recurring Cerebral Infarction.
timeFrame: For 90 days of the treatment period.
Other outcomes:
Locations:
city: Arkhangelsk
country: Russian Federation
facility: The First City Clinical Hospital named after E.E. Volosevich
city: Arkhangelsk
country: Russian Federation
facility: Arkhangelsk Regional Clinical Hospital/Neurological Department
city: Belgorod
country: Russian Federation
facility: Belgorod Regional Clinical Hospital of St. Joasaph
city: Chelyabinsk
country: Russian Federation
facility: Regional Clinical Hospital # 3
city: Kazan
country: Russian Federation
facility: Kazan State Medical University/Republican Clinical Hospital of the Ministry of Health of the Republic of Tatarstan
city: Kazan
country: Russian Federation
facility: Interregional Clinical Diagnostic Center
city: Kazan
country: Russian Federation
facility: City Clinical Hospital # 7
city: Krasnodar
country: Russian Federation
facility: Research Institute - Regional Clinical Hospital # 1 named after Prof. S.V. Ochapovsky
city: Moscow
country: Russian Federation
facility: City Clinical Hospital named after V.M. Buyanov, Moscow Department of Health
city: Moscow
country: Russian Federation
facility: Central Clinical Hospital of the Russian Academy of Sciences
city: Nizhny Novgorod
country: Russian Federation
facility: City Clinical Hospital # 5 of the Nizhegorodskiy District of Nizhny Novgorod
city: Novosibirsk
country: Russian Federation
facility: Novosibirsk State Regional Clinical Hospital
city: Ryazan
country: Russian Federation
facility: Regional Clinic Hospital/Emergency cardiology unit with intensive care and resuscitation unit
city: Saint Petersburg
country: Russian Federation
facility: St. Petersburg Research Institute of Ambulance named after I.I. Janelidze
city: Saint Petersburg
country: Russian Federation
facility: City Multidisciplinary Hospital # 2
city: Samara
country: Russian Federation
facility: Samara City Clinical Hospital # 1 named after N.I. Pirogov/Neurological Department
city: Saratov
country: Russian Federation
facility: Saratov City Clinical Hospital # 9
city: Ulyanovsk
country: Russian Federation
facility: Ulyanovsk Regional Clinical Hospital/Neurological Department
city: Vladimir
country: Russian Federation
facility: Regional Clinic Hospital/Neurological department for patients with acute cerebrovascular accident
city: Voronezh
country: Russian Federation
facility: Voronezh Regional Clinical Hospital # 1
city: Vsevolozhsk
country: Russian Federation
facility: Vsevolozhsk Clinical Interdistrict Hospital
city: Yaroslavl
country: Russian Federation
facility: Clinical Hospital # 8/Intensive Care Unit
Study officials:
References: