Effects of Cerebrolysin Combined With Rehabilitation on Motor Recovery in Stroke

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

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.

Study Overview

• Status: Completed
• Conditions: Stroke
• Intervention / Treatment: Drug: Cerebrolysin; Drug: Placebo

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Samsung Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. The first-ever stroke (ischemic)
2. Confirmed by CT or MRI
3. Subacute stage: less than 1 week
4. Severe motor function involvement (FMA < 50)
5. Age: between 19 and 80 years
6. Inpatients
7. Written informed consent obtained from the patient or legally authorized representative

Exclusion Criteria:

1. Contraindication of MRI
2. Progressive or unstable stroke
3. Pre-existing and active major neurological disease
4. Pre-existing and active (e.g., on chronic medication) major psychiatric disease, such as major depression, schizophrenia, bipolar disease, or dementia
5. A history of significant alcohol or drug abuse in the prior 3 years
6. Advanced liver, kidney, cardiac, or pulmonary disease
7. A terminal medical diagnosis consistent with survival < 1 year
8. Substantial decrease in alertness at the time of randomization, defined as score of 2 on NIH Stroke Scale
9. Pregnancy or lactating; note that a negative pregnancy test will be required if the patient is a female in reproductive years
10. Any condition that would represent a contraindication to Cerebrolysin, including allergy to Cerebrolysin
11. Current enrolment in another therapeutic study of stroke or stroke recovery
12. 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.
13. Previous porcine brain peptide administration history

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cerebrolysin; 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); Rehabilitation3 hours (physiotherapy: 2 hours, occupational therapy: 1 hour) / day5 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; Cerebrolysin- cerebrolysin 30 ml with 100 ml dilution/day * 21 days with rehabilitation; Other Names: Porcine brain peptide
Placebo Comparator: Placebo; 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); Rehabilitation3 hours (physiotherapy: 2 hours, occupational therapy: 1 hour) / day5 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; Placebo- saline 100 ml/day * 21 days with rehabilitation; Other Names: Saline

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Samsung Medical Center
• Collaborators: Ever Neuro Pharma GmbH

Study record dates

Study Major Dates

• Study Start (Actual): March 14, 2016
• Primary Completion (Actual): February 14, 2019
• Study Completion (Actual): February 14, 2019

Study Registration Dates

• First Submitted: March 4, 2016
• First Submitted That Met QC Criteria: May 10, 2016
• First Posted (Estimate): May 11, 2016

Study Record Updates

• Last Update Posted (Actual): September 20, 2019
• Last Update Submitted That Met QC Criteria: September 18, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: cerebrolysin, stroke, motor function
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Physiological Effects of Drugs; Neuroprotective Agents; Protective Agents; Nootropic Agents; Cerebrolysin
• Other Study ID Numbers: 2015-10-034

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No