Effects of Cerebrolysin Combined With Rehabilitation on Motor Recovery in Stroke

Study Overview
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Brief Summary
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This study, E-COMPASSII is a phase IV clinical trial designed as a multicenter, randomized, double-blind, placebo-controlled, parallel-group study. This study will enroll 80 subacute stroke patients with severe motor involvement. Primary objective is to demonstrate the efficacy of porcine brain peptide to improve motor recovery measured by the improvement ratio of Fugl-Meyer assessment ((score of FMA after 3 weeks - score of FMA at baseline) / score of FMA at baseline) in patients with subacute stroke. Secondary objectives are to evaluate the safety profile of cerebrolysin and to test the hypothesis that subacute stroke patients with severe motor involvement randomized to administration of Cerebrolysin combined with rehabilitation for 3 weeks show better outcome on global function (Korean version Modified Barthel Index, K-MBI), severity of stroke (National Institute of Health Stroke Scale, NIHSS), cognitive function (Korean Version of Mini-Mental State Exam, K-MMSE; Korean version Montreal Cognitive Assessment, K-MoCA), upper limb function (Action Research Arm Test, ARAT; Box and block test, B&B) and neuroplasticity measure (resting-state functional MRI(rsfMRI), diffusion tensor image(DTI), and motor evoked potential(MEP)) at 3 months after stroke.

Detailed Description
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Randomized double-blinded, placebo-controlled multicenter study with two treatment groups Number of Patients: 80 patients (n = 40 per group) 5 study centers will participate in this study. Group 1(Cerebrolysin): cerebrolysin 30 ml with 100 ml dilution/day * 21 days with rehabilitation Group 2(Placebo): saline 100 ml/day * 21 days with rehabilitation

Official Title
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Effects of Cerebrolysin Combined With Rehabilitation on Motor Recovery in Patients With Severe Motor Involvement at Subacute Phase of Stroke

Conditions
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Stroke

Intervention / Treatment
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* Drug: Cerebrolysin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The first-ever stroke (ischemic) Confirmed by CT or MRI Subacute stage: less than 1 week Severe motor function involvement (FMA < 50) Age: between 19 and 80 years Inpatients Written informed consent obtained from the patient or legally authorized representative Exclusion Criteria: Contraindication of MRI Progressive or unstable stroke Pre-existing and active major neurological disease Pre-existing and active (e.g., on chronic medication) major psychiatric disease, such as major depression, schizophrenia, bipolar disease, or dementia A history of significant alcohol or drug abuse in the prior 3 years Advanced liver, kidney, cardiac, or pulmonary disease A terminal medical diagnosis consistent with survival < 1 year Substantial decrease in alertness at the time of randomization, defined as score of 2 on NIH Stroke Scale Pregnancy or lactating; note that a negative pregnancy test will be required if the patient is a female in reproductive years Any condition that would represent a contraindication to Cerebrolysin, including allergy to Cerebrolysin Current enrolment in another therapeutic study of stroke or stroke recovery Total serum bilirubin > 4 mg/dL, alkaline phosphatase > 250 U/L, SGOT/AST > 150 U/L, SGPT/ALT > 150 U/L, or creatinine > 3.5 mg/dL; or cardiopulmonary deficits large enough to interfere with reasonable participation in physiotherapy during the trial. Previous porcine brain peptide administration history

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cerebrolysin<br>Cerebrolysin 30 ml with 100 ml dilution/day * 21 days with rehabilitation Study drug schedule - given from day 8 after stroke, but, if day 8 is weekend, the given day is the next Monday(day 9 10) Rehabilitation 3 hours (physiotherapy: 2 hours, occupational therapy: 1 hour) / day 5 times/week for 3 weeks Duration of Treatment: Study drug will be given once daily by intravenous infusion for 21 consecutive days on study day 8   28. The clinical observation period for each patient will be 90 days and will include four clinical evaluation visits at Screening(day ≤ 7), Baseline(day 8) and on study day 29, and 90. | Drug: Cerebrolysin<br>* Cerebrolysin- cerebrolysin 30 ml with 100 ml dilution/day * 21 days with rehabilitation<br>* Other names: Porcine brain peptide;|
| Placebo Comparator: Placebo<br>Saline 100 ml/day * 21 days with rehabilitation Study drug schedule - given from day 8 after stroke, but, if day 8 is weekend, the given day is the next Monday(day 9 10) Rehabilitation 3 hours (physiotherapy: 2 hours, occupational therapy: 1 hour) / day 5 times/week for 3 weeks Duration of Treatment: Study drug will be given once daily by intravenous infusion for 21 consecutive days on study day 8   28. The clinical observation period for each patient will be 90 days and will include four clinical evaluation visits at Screening(day ≤ 7), Baseline(day 8) and on study day 29, and 90. | Drug: Placebo<br>* Placebo- saline 100 ml/day * 21 days with rehabilitation<br>* Other names: Saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Score of Fugl-Meyer assessment (FMA) | Motor function | 3 months after stroke | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Score of Korean version Modified Barthel Index (K-MBI) | Global function | 3 months after stroke | 
| Score of National Institute of Health Stroke Scale (NIHSS) | Severity of stroke | 3 months after stroke | 
| Score of Korean Version of Mini-Mental State Exam(K-MMSE) and Korean version of Montreal Cognitive Assessment (K-MoCA) | Cognitive function | 3 months after stroke | 
| Score of Action Research Arm Test (ARAT) and box and block test | Upper limb function | 3 months after stroke | 
| Score of EuroQol (EQ-5D) | Quality of life | 3 months after stroke | 
| Days of Length of hospital stay |  | 3 months after stroke | 
| Brain activation of resting-state functional MRI | Neuroplasticity measure | 3 months after stroke | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cerebrolysin, stroke, motor function