Condition category
Circulatory System
Date applied
Date assigned
Last edited
Prospectively registered
Overall trial status
Recruitment status
Not yet recruiting

Plain English Summary

Post-stroke cognitive impairment is a particularly serious consequence of cerebral ischemia and often inhibits or retards patient rehabilitation. The prevalence of post-stroke cognitive impairment ranges between 20-80%.
This is a study to investigate the effects of Cerebrolysin treatment on the recovery of patients with post-stroke cognitive impairment. The rationale of the study is based on the previously documented neuroprotective characteristics of Cerebrolysin with potential of preventive effects for cognitive decline after stroke.

Who can participate?
Adults between 40 and 80 years with acute ischemic stroke with onset 72 hours prior to screening.

What does the study involve?
Participants are invited to join this study at 72 hours post stroke onset. After informing patients about study procedures, benefits and potential risks, they sign a consent form. All participants included in the study must pass the screening criteria and baseline evaluations. Individuals are then allocated to one of two groups. The first group is administered Cerebrolysin 30 ml/day in four treatment cycles of ten days, while the second group receives placebo, following the same schedule.

What are the possible benefits and risks of participating?
Potential benefit of Cerebrolysin administration is the improved cognitive function and brain recovery in patients with stroke. The main risk for patients is developing adverse events (AE). Their severity and the causality to study medication is carefully assessed in order to establish a detailed safety profile of the intervention.

Where is the study run from?
CODEC is a trial run from Cluj-Napoca (Romania)

When has the study started and how long is it expected to run for?
May 2020 to May 2024

Who is funding the study?
The Society for the Study of Neuroprotection and Neuroplasticity (SSNN) (Romania)

Who is the main contact?
Dr Olivia Verisezan Rosu

Trial website

Contact information



Primary contact

Prof Dafin Fior Muresanu


Contact details

37 Mircea Eliade Street



Additional contact

Dr Olivia Verisezan Rosu


Contact details

37 Mircea Eliade Street

Additional identifiers

EudraCT number

Nil known number

Nil known

Protocol/serial number


Study information

Scientific title

A randomized, placebo-controlled, double-blind trial to asses the effficacy and safety of CEREBROLYSIN in the treatment of Post-Stroke Cognitive Decline



Study hypothesis

Patients randomized to Cerebrolysin will show improved cognitive outcome measured with a battery of co-primary neuropsychological tests as compared to patients randomized to placebo.

Ethics approval

Approved 27/03/2020, Ethics Committee of the Iuliu Hatieganu University of Medicine and Pharmacy (8 Babeş Street, 400012 Cluj-Napoca, Romania; +40-264-597-256;, ref: 121/24.03.2020

Study design

Randomized, placebo-controlled, double-blind, phase IV study

Primary study design


Secondary study design

Randomised controlled trial

Trial setting


Trial type


Patient information sheet

No participant information sheet available


Radiologically confirmed acute ischemic stroke with onset within 72 hours prior to screening


The synopsis of the study is organised in 4 visits:
1. Visit 1: Screening Part 1 - Study Day -30 (within 72 hours after stroke onset)
2. Visit 2: Screening Part 2 & Baseline - Study Day 0
3. Visit 3 - Study Day 180
4. Visit 4 - Study Day 360

No follow-up will be performed after the 360-day evaluation. The study arms will be administered the following treatment courses:
1. Treatment Group: Cerebrolysin Solution 30 ml diluted with 0.9% saline solution to 250 ml, administered by IV infusion
2. Placebo Group: 250 ml 0.9% saline solution administered by IV infusion

Treatment Cycle 1: Study day 1 – 10; 10 Infusions, once daily
Treatment Cycle 2: Study day 61-70; 10 Infusions, once daily
Treatment Cycle 3: Study day 121-130; 10 Infusions, once daily
Treatment Cycle 4: Study day 241-250; 10 Infusions, once daily

Randomisation and Blinding:
This study will be performed under double-blind conditions to keep investigators, other study personnel and patients blinded to treatment allocation. Cerebrolysin is an amber-colored solution. Therefore, colored infusion lines will be used for drug administration.

Patients meeting in- and exclusion criteria will obtain a random number corresponding to the random list generated in advance by a biometrician selected by the coordinator. Patients will be randomly allocated to the study groups in a 1:1 ratio.

A balanced random code list is prepared using the random permuted block scheme. In accordance with the ICH Biostatistics Guideline, the block size is intentionally not given in the study protocol.

The sealed random code list and the sets of sealed envelopes are prepared using the validated program RANCODE in a validated working environment at idv Data Analysis and Study Planning, Gauting, Germany. Sealed emergency envelopes will be provided to the Study Safety Officer (SSO) as well as to the Principle Investigator and the Study Nurse responsible for the preparation of the study medication.

The person who prepares the infusion at the study center will be independent of all other study specific procedures, in particular any safety or efficacy assessments and the study nurse is not allowed to disclose any information about treatment allocation.

The randomization envelope will be opened by the nurse at the time when the patient’s first ready-to-use-infusion is being prepared. The double-blind study medication labels of the ready-to-use-infusion will identify only the unique randomization number which is the same as the patient number.

The whole study will be unblinded after closure of the database and determination of the analysis populations.

Intervention type



Phase IV

Drug names


Primary outcome measure

1. Cognitive function assessed using Stroop Color-Word Test (Stroop, 1935) at 0, 180, 360 days
2. Cognitive function assessed using Trail Making Test Part A (Reitan, 1958) at 0, 180, 360 days
3. Cognitive function assessed using Digit Span Backwards Task (Wechsler adult intelligence scale – third edition) (Wechsler, 1997) at 0, 180, 360 days
4. Cognitive function assessed using Verbal Fluency Test – CFL Version (Benton & Hamsher, 1976) at 0, 180, 360 days
5. Cognitive function assessed using Digit Symbol (Wechsler adult intelligence scale – third edition) (Wechsler, 1997) at 0, 180, 360 days
6. Cognitive function assessed using Rey Auditory Verbal Learning Test (Rey, 1964) at 0, 180, 360 days

Secondary outcome measures

1. Cognitive function assessed using Montreal Cognitive Assessment (MoCA) (Nasreddine, 2005) at 0, 180, 360 days
2. Stroke severity assessed by NIH Stroke Scale ( at 0, 180, 360 days
3. Functional outcome assessed by Modified Rankin Score (van Swieten J et al., 1988) at 0, 180, 360 days
4. Emotional status assessed using Hospital Anxiety and Depression Scale (Zigmond, 1983) at 0, 180, 360 days
5. Functional outcome assessed using EQ-5D-5L (Herdman, 2011)at 0, 180, 360 days

Overall trial start date


Overall trial end date


Reason abandoned (if study stopped)


Participant inclusion criteria

1. Acute Ischemic Stroke confirmed by CT
2. Stroke is ischemic in origin - TACS or PACS
3. Onset of Stroke within 72 hours prior to screening
4. NIH Stroke Scale score between 5 and 15
5. Pre-stroke mRS of 0 or 1
6. No cognitive impairment prior to stroke with an IQ code score < 3
7. Age between 40 and 80 years, inclusive
8. Diagnosis of stroke ischemic in origin confirmed by MRI

Participant type


Age group




Target number of participants


Participant exclusion criteria

1. Previous ischemic stroke or intracranial hemorrhage not related to the index stroke or previous TIA
2. Severe visual or hearing impairment interfering with psychometric test procedures
3. Pre-existing and active major neurological disease (eg. Parkinson’s Disease, Epilepsy)
4. Pre-existing and active major psychiatric disease, such as major depression, schizophrenia, bipolar disease, or dementia
5. History of significant alcohol or drug abuse
6. Advanced liver, kidney, cardiac, or pulmonary disease
7. A terminal medical diagnosis with survival < 1 year
8. Pregnancy or lactating
9. Any contraindications to Cerebrolysin
10. Current enrolment in another therapeutic study
11. Dementia due to strategic index stroke
12. Major communication deficits with a Goodglass & Kaplan Score > 2
13. Aphasia with an NIHSS Item 9 score of > 2
14. Treatment with Cerebrolysin or Neuroprotectants in the last 30 days
15. Severe dementia with MMSE Score < 12

Recruitment start date


Recruitment end date



Countries of recruitment


Trial participating centre

“RoNeuro” Institute for Neurological Research and Diagnostic
37 Mircea Eliade Street

Sponsor information


The foundation for the study of neuroscience and neuroregeneration

Sponsor details

(RO: Fundatia pentru Studiul Nanoneurostiintelor si Neuroregenerarii)
37 Mircea Eliade Street

Sponsor type

Research organisation



Funder type

Research organisation

Funder name

The foundation for the study of neuroscience and neuroregeneration

Alternative name(s)

Funding Body Type

Funding Body Subtype


Results and Publications

Publication and dissemination plan

Planned publication in a high-impact peer-reviewed journal

IPD sharing statement:
The data sharing plans for the current study are unknown and will be made available at a later date.

Intention to publish date


Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

16/04/2020: Trial’s existence confirmed by the Ethics Committee of the Iuliu Hatieganu University of Medicine and Pharmacy.