Clinical trial NCT06437626: The Study of Efficacy and Safety of Mexidol® in Stroke Therapy (MIR)
Official title: Prospective International Multicenter Randomized, Double-blind, Placebo-controlled, Parallel-group Study of the Efficacy and Safety of Mexidol® in Sequential Treatment of Patients in the Acute and Early Recovery Periods of Ischemic Stroke
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Ischemic Stroke
Keywords: Stroke
Ischemic Stroke
Neuroprotective Agents
Nootropic Agents
Antioxidants
Randomized Controlled Trials as Topic
Stroke Rehabilitation
Recovery of Function
Brain Ischemia
Acute Stroke
Acute Cerebrovascular Accident
Cerebral Stroke
Neuroprotection
Mexidol
Ethylmethylhydroxypyridine Succinate
Lead sponsor: Pharmasoft
Sponsor class: INDUSTRY
First posted: 2024-05-31
Enrollment: 304
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 main purpose of the clinical trial is to assess efficacy and safety of Mexidol® in sequential treatment (solution for intravenous and intramuscular administration 50 mg/ml + film-coated tablets 250 mg) of patients in the acute and early recovery periods of ischemic stroke.

Detailed description: As the main purpose of the clinical study is to evaluate safety and efficacy of a neuroprotector (Mexidol®), it was crucial to develop strict protocol requirements that would help to avoid the challenges of estimation of neuroprotective effect for stroke therapy. The current treatment options for stroke are still limited and do not take into account rehabilitation period and patients' further quality of life.

As per protocol requirements, 313 participants were screened, 304 participants met all comprehensive eligibility criteria, 24 participants dropped out during the clinical trial period. The Modified Rankin Scale (mRS) was selected as the most representative primary outcome measuring tool due to the adequate representation of functional outcome. Additionally, the neuroprotective efficacy of Mexidol® was assessed for its ability to reduce stroke-related neurologic deficit and mood disorder symptoms, cognitive impairment, and to improve mobility after stroke.

Eligibility criteria: Inclusion Criteria:

* Clinical diagnosis of first-ever hemispheric ischemic stroke (codes ICD-10: I63.0 - I63.9) with the time from onset of a stroke \<48 hours.
* CT or MRI evidences of clinical diagnosis and no evidences of hemorrhagic stroke/hemorrhagic transformation of ischemic stroke.
* The written informed consent form (ICF) is signed and personally dated by the participant or by an impartial witness (by a person who is independent of the trial and cannot be unduly influenced by the people involved with the trial and who attends the informed consent process).
* The Modified Rankin Scale (mRS) score ≥3.
* The National Institutes of Health Stroke Scale (NIHSS) score from 9 to 15 points.
* Negative pregnancy test for women of childbearing age.
* Willingness to use reliable methods of contraception, and/or abstinence, for the duration of therapeutic product exposure.
* The ability to understand the purpose of research, risks associated with the research intervention, obligations and consequences of research participation and their right of withdrawing consent any time during the study.

Exclusion Criteria:

* BMI (Body Mass Index) \> 35.
* Recurrent or hemorrhagic stroke confirmed by CT/MRI.
* Hemorrhagic transformation of ischemic stroke.
* Parkinson's disease/parkinsonism.
* Progressive Multiple Sclerosis.
* Intractable Epilepsy.
* Demyelinating diseases of central nervous system.
* Hereditary and degenerative diseases of the central nervous system.
* Infectious diseases of central nervous system in medical history.
* Traumatic brain injury with severe neurocognitive impairment in medical history.
* Congenital malformations of the nervous system or any neurological disorders that can affect participant's capability (including cognitive and motor skills) to follow protocol procedures.
* Thrombolysis or thrombectomy treatment prior the enrollment.
* Medical history of severe allergies.
* Evidence of hypersensitivity reactions or intolerance associated with ethylmethylhydroxypyridine.
* Evidence of lactose intolerance, galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption.
* Acute surgical pathology.
* Evidence of clinically significant first identified disorder or disease that can affect participant's ability to participate in the clinical trial.
* Evidence of clinically significant severe disease/condition that can affect participant's ability to participate in the clinical trial: respiratory diseases, cardiovascular diseases (CVDs) including SAP ≥ 200 mm Hg and DAP ≥ 100 mm Hg, liver disease with elevation of ALT/AST \> 2 × ULN, kidney disease (еGFR\<30ml/min/1.73 m2), endocrine disorders and diseases, gastrointestinal diseases, pulmonary embolism (PE), deep vein thrombosis (DVT), floating thrombus, convulsive syndrome, uncontrolled hyperthermia, uncontrolled hyperglycemia.
* Medical history of severe mental disorder.
* Dementia of the Alzheimer type (DAT).
* Medical history of cancers within 5 years prior to enrollment.
* Medical history of alcohol/drug addiction.
* Pregnancy or breastfeeding.
* Prescription or use of prohibited medications within 2 weeks prior to enrollment.
* Positive HIV, syphilis, hepatitis B and C test.
* Positive COVID-19 test.
* Participation in another trial within 3 months prior to enrollment.

Primary outcomes:
measure: Change from Baseline (Visit 0, Day 0-1) in Modified Rankin Scale (mRS) scores at Visit 4 (Day 71(+2))
timeFrame: Baseline, Day 71
Secondary outcomes:
measure: Percentage of subjects having Modified Rankin Scale (mRS) scores >3 (higher degree of disability) at Visit 4 (Day 71(+2))
timeFrame: Day 71
measure: Percentage of subjects having Modified Rankin Scale (mRS) scores 0-1 (normal or lower degree of disability) at Visit 4 (Day 71(+2))
timeFrame: Day 71
measure: Change from Baseline (Visit 0, Day 0-1) in the National Institutes of Health Stroke Scale (NIHSS) score at Visit 4 (Day 71(+2))
timeFrame: Baseline, Day 71
measure: Change from Baseline (Visit 1, Day 1) in the Rivermead Mobility Index (RMI) score at Visit 4 (Day 71(+2))
timeFrame: Baseline, Day 71
measure: Change from Baseline (Visit 1, Day 1) in the Montreal Cognitive Assessment (MoCA) score at Visit 4 (Day 71(+2))
timeFrame: Baseline, Day 71
measure: Change from Baseline (Visit 1, Day 1) in the Hospital Anxiety and Depression Scale (HADS) score at Visit 4 (Day 71(+2))
timeFrame: Baseline, Day 71
Other outcomes:
Locations:
city: Almaty
country: Kazakhstan
facility: Almaty City Hospital № 7
city: Kazan
country: Russian Federation
facility: Tatarstan Republican Clinical Hospital
city: Kazan
country: Russian Federation
facility: Interregional Clinical Diagnostic Center
city: Kazan
country: Russian Federation
facility: Kazan City Hospital № 7
city: Kemerovo
country: Russian Federation
facility: Kemerovo City Clinical Hospital № 11
city: Krasnodar
country: Russian Federation
facility: Research Institute - Regional Clinical Hospital № 1
city: Moscow
country: Russian Federation
facility: Federal Center for Brain and Neurotechnology
city: Moscow
country: Russian Federation
facility: Russian National Research Medical University n.a. N. I. Pirogov
city: Rostov-on-Don
country: Russian Federation
facility: Rostov State Medical University
city: Saint Petersburg
country: Russian Federation
facility: Alexandrovskaya Hospital
city: Saint Petersburg
country: Russian Federation
facility: St. Petersburg Clinical Hospital № 26
city: Saint Petersburg
country: Russian Federation
facility: National Medical Research Center n.a. V. A. Almazov
city: Saint Petersburg
country: Russian Federation
facility: City Hospital № 40 of Kurortny District
city: Samara
country: Russian Federation
facility: Samara Regional Clinical Hospital n.a. V. D. Seredavin
city: Ulyanovsk
country: Russian Federation
facility: Central Clinical Medical and Sanitary Unit n.a. V. A. Egorov
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: Yaroslavl Clinical Hospital № 2
city: Tashkent
country: Uzbekistan
facility: The first clinic of the Tashkent Medical Academy
Study officials:
References: