Condition category
Circulatory System
Date applied
10/04/2020
Date assigned
29/04/2020
Last edited
29/04/2020
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
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
olivia.rosu@ssnn.ro

Trial website

Contact information

Type

Scientific

Primary contact

Prof Dafin Fior Muresanu

ORCID ID

http://orcid.org/0000-0002-9536-1153

Contact details

37 Mircea Eliade Street
Cluj-Napoca
400364
Romania
+40740066761
dafinm@ssnn.ro

Type

Public

Additional contact

Dr Olivia Verisezan Rosu

ORCID ID

Contact details

37 Mircea Eliade Street
Cluj-Napoca
400364
Romania
+40744820493
olivia.rosu@ssnn.ro

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

FSNANO100220

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

Acronym

CODEC

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; contact@umfcluj.ro), ref: 121/24.03.2020

Study design

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

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

No participant information sheet available

Condition

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

Intervention

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

Drug

Phase

Phase IV

Drug names

Cerebrolysin

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 (http://www.nihstrokescale.org/) 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

20/02/2020

Overall trial end date

01/05/2024

Reason abandoned (if study stopped)

Eligibility

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

Patient

Age group

Adult

Gender

Both

Target number of participants

290

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

01/06/2020

Recruitment end date

31/05/2023

Locations

Countries of recruitment

Romania

Trial participating centre

“RoNeuro” Institute for Neurological Research and Diagnostic
37 Mircea Eliade Street
Cluj-Napoca
400364
Romania

Sponsor information

Organisation

The foundation for the study of neuroscience and neuroregeneration

Sponsor details

(RO: Fundatia pentru Studiul Nanoneurostiintelor si Neuroregenerarii)
37 Mircea Eliade Street
Cluj-Napoca
400364
Romania
+40740150076
office@ssnn.ro

Sponsor type

Research organisation

Website

https://www.ssnn.ro/

Funders

Funder type

Research organisation

Funder name

The foundation for the study of neuroscience and neuroregeneration

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

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

01/12/2024

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.