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Stroke, IschemicPhase 3NCT04904341

Efficacy of Cerebrolysin Treatment as an add-on Therapy to Mechanical Thrombectomy in Acute Ischemic Stroke.

A Phase 3 study testing Cerebrolysin in people with Stroke, Ischemic and Stroke, Acute, run by Military Institute od Medicine National Research Institute at 1 site in Poland.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

This study is designed to determine the efficacy and safety of Cerebrolysin treatment as an add- on therapy to mechanical thrombectomy (MT) in reducing global disability in subjects with acute ischemic stroke (AIS). Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Stroke, Ischemic, Stroke, Acute, Stroke Sequelae
What is being tested?
Cerebrolysin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
1 sitePoland
Study dates
1 Jan 2021to 31 Dec 2024
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Clinical Inclusion Criteria:
  • Age 18-80 years
  • Signs and symptoms consistent with the diagnosis of an anterior circulation AIS
  • Stroke onset to groin ≤6h (stroke onset is defined as the time the patient was last known to be at their neurologic baseline (wake-up strokes are eligible if they meet the above time limits).
  • mRS ≤1 prior to qualifying stroke (functionally independent for all ADLs)
  • moderate to severe stroke: NIHSS score of ≥5 with presence of any cortical signs (gaze, visual fields, language, or neglect)
Show all 14Show fewer
  • Initiation of treatment with Cerebrolysin ≤8h following stroke onset (Cerebrolysin group)
  • Patient has signed the Informed Consent form (Cerebrolysin group)
  • Neuroimaging Inclusion Criteria:
  • CT ASPECTS ≥6 prior to MT
  • ICA or MCA-M1 or -M2 occlusion (carotid occlusions can be cervical or intracranial; without tandem MCA lesions) by CTA
  • Target mismatch profile on CTP (ischemic core volume <70 ml, mismatch ratio ≥1.8 (ischemic penumbra at least 180% larger than the ischemic core volume) and mismatch volume ≥15 ml)
  • Moderate-to-good collateral status on multiphase CTA (>50% MCA territory)
  • Effective reperfusion mTICI ≥2b following MT

Who cannot join

  • Clinical Exclusion Criteria:
  • Other serious, advanced, or terminal illness or life expectancy ≤ 6 months
  • Pre-existing medical, neurological or psychiatric disease that would confound the neurological or functional evaluations (e.g. Alzheimer's disease, vascular dementia, Parkinson's disease, demyelinating disease, encephalopathy of any cause,a history of significant alcohol or drugabuse)
  • Pregnancy or lactation
  • Known allergy to iodine that precludes an endovascular procedure
  • Acute or chronic renal failure with calculated creatinine clearance <30 ml/min/1.73m2 or unable to undergo a contrast brain perfusion scan withCT
Show all 14Show fewer
  • Inability to tolerate or comply with studyprocedures
  • Any condition that would represent a contraindication for Cerebrolysin administration (e.g.allergy)
  • Neuroimaging Exclusion Criteria:
  • Acute symptomatic arterial occlusions in more than one vascular territory confirmed on CTA (e.g., bilateral MCA occlusions, or an MCA and a basilar artery occlusion)
  • Evidence of intracranial tumor (except small meningioma) acute intracranial hemorrhage, neoplasm, or arteriovenous malformation
  • Significant mass effect with midline shift
  • Treatment with another investigational drug within the last 30 days that may interfere with this study's medications
  • Patients with nondiagnostic NCCT or CTP maps

Trial locations and contacts

1 site in 1 country.

Jacek Staszewski, MD, PhD contact

+48261816445

jstaszewski@wim.mil.pl

Poland1 site, 1 recruiting
  • Military Institute of Medicine

    Warsaw, Masovian Voivodeship, 04-141

    Jacek Staszewski, MD, PhD, 607871754, jacekstaszewski@wp.pl

    Piotr Piasecki, MD, PhD

    Recruiting

Other trials in Poland

About this study

Official title: Efficacy of Cerebrolysin Treatment as an add-on Therapy to Mechanical Thrombectomy in Patients With Acute Ischemic Stroke Due to Large Vessel Occlusion - a Prospective, Open Label, Single Center Study With 12 Months of Follow-up.

This study is designed to determine the efficacy and safety of Cerebrolysin treatment as an add- on therapy to mechanical thrombectomy (MT) in reducing global disability in subjects with acute ischemic stroke (AIS). The investigators have planned a single centre, prospective, open-label, single-arm study with 12 months follow-up of 50 patients with moderate to severe AIS, with a small established infarct core and with good collateral circulation who achieve significant reperfusion following MT and who receive additional Cerebrolysin within 8 hours of stroke onset compared to 50 historical controls treated with MT alone - matched for age, clinical severity, occlusion location, baseline perfusion lesion volume, onset to reperfusion time and use of iv thrombolytic therapy (rt-PA).

The primary outcome measure will be overall proportion of subjects receiving Cerebrolysin comparing to control group experiencing a favorable functional outcome (by modified Rankin Scale [mRS] 0-2) at 7 day, 30 days, 90 days and 12 months following stroke onset. The secondary objectives are to determine the efficacy of Cerebrolysin as compared to control group in reducing risk of symptomatic secondary hemorrhagic transformation, improving neurological outcome (NIHSS 0-2 at day 7, day 30 and 90); reducing mortality rates (over the 90-day and 12 months study period); and improving: activities of daily living (by Barthel Index; BI), health-related quality of life (as measured by the EQ-5D-5L) assessed at day 30, 90 and at 12 months. The other measures of efficacy in Cerebrolysin group will include: assessment of final stroke volume and penumbral salvage (measured by CT/CTP at 30 days) and its change compared to baseline volume, changes over time in language function (by the 15-item Boston Naming Test), hemispatial neglect (by line bisection test), global cognitive function (by The Montreal Cognitive Assessment) and depression (by Hamilton Depression Rating Scale) between day 30 and day 90 assessments). The patients will receive 30 ml of Cerebrolysin within 8h of AIS stroke onset and continue treatment once daily until day 21 (first cycle) and they will receive a second cycle of treatment (30 ml/d for 21 days given in the Outpatient Department or Neurorehabilitation Clinic) from day 69 to 90 (± 3 days). All the patients (including those from the control group) receive the same standardized rehabilitation program (including speech therapy, occupational and physical therapy) during hospitalization at Stroke Unit and at Neurorehabilitation Clinic until day 90 according to local procedures. Historical data will be obtained by retrospective clinical chart reviews of patients hospitalized in the study center between Jan.2018 and Dec.2020 and fulfilling the same clinical and radiological inclusion criteria in whom 12-month follow-up (including mRS, NIHSS, BI, EQ-5D-5L) could be obtained.

Read the detailed description

Background

The recent endovascular stroke trials have established a new paradigm for acute ischemic stroke (AIS) treatment showing that mechanical thrombectomy (MT) within 6 hours of stroke significantly reduces the mortality rate and improves clinical outcomes. These positive results were not only driven by improved endovascular devices, but also by a refinement of patient selection criteria, including the use of perfusion and collaterals status. Despite these advances, the rates of functional independence (14%-58%) following MT are poor compared with the efficient rates of recanalization (60%-90%). The mechanisms underlying this "no-reflow phenomenon" are thought to result from altered microvascular circulation, proinflammatory state and thrombosis that can persist despite proximal recanalization.

Mechanical revascularization presents a proven procedure with no potential drug-drug interactions, that can be administered in series or parallel with neuroprotective agents. Cerebrolysin is a neuropeptide preparation produced by standardized enzymatic breakdown of porcine brain proteins. In experimental AIS studies Cerebrolysin has been shown to reduce the infarction volume, proinflammatory cytokines, improve brain-blood-barrier dysfunction induced by rt-PA and enhance functional recovery.

The investigators have hypothesized that adding Cerebrolysin in selected patients based on the clinical and radiological criteria (baseline small ischemic core, good collateral status, significant reperfusion following MT, symptoms of cortical damage) may increase the effectiveness of MT by initiating cytoprotective effects and preventing reperfusion injury and delayed cell death. The multimodal treatment concept (Cerebrolysin combined with MT in acute stroke and combined with rehabilitation in post-acute period) might also promote the most effective recovery from moderate-to-severe stroke.

Aim

The aim of this study is to evaluate the efficacy and safety of Cerebrolysin treatment as an add-on therapy to MT in patients with AIS in the early recovery phase in acute ischemic stroke (90 days) and in long-term follow-up (12 months).

Methods and Patients

A single centre, prospective, open-label, single-arm study of consecutive 50 patients who will be treated with MT in the reference centre according to local standards and additional Cerebrolysin compared to 50 historical controls treated with MT alone - matched for age, clinical severity, occlusion location, baseline perfusion lesion volume, onset to reperfusion and use of iv rt-PA prior to MT.

The first Cerebrolysin infusion (30 ml mixed with 250 mL of saline) is intended to be initiated as soon as possible after successful recanalization is achieved and within 8h of AIS stroke onset. Cerebrolysin treatment will be continued (30 ml/d) once daily until day 21 (first cycle) and followed by a second cycle of treatment (30 ml/d for 21 days given in the Outpatient Department or Neurorehabilitation Clinic) from day 69 to 90 (± 3 days).

All the patients (including those from the control group) will receive the same standardized rehabilitation program (including speech therapy, occupational and physical therapy) during hospitalization at Stroke Unit and at Neurorehabilitation Clinic until day 90 according to local procedures.

Patients will undergo imaging at baseline, prior to mechanical thrombectomy. This will include non-contrast CT (NCCT), CT angiography (CTA) and CT perfusion (CTP) acute stroke imaging for prospectively enrolled patients. Follow up NCCT will be acquired at 24 hours and 30 days. Automated processing of NCCT, CTA and CTP will be performed using the latest CE-marked version of e-Stroke software (Brainomix, Oxford, UK) at baseline, and follow up imaging will be processed using algorithms in development by Brainomix. This will provide objective and consistent quantification of imaging biomarkers to ensure robust matching to historical controls as outlined in the study protocol, as well as evaluation of imaging endpoints. NCCT, CTA and CTP will be processed using e-ASPECTS,e-CTA, and e-CTP modules within e-Stroke respectively. Historical control patients will have had NCCT and CTA as a minimum, and CTP will be included wherever possible.

Historical data will be obtained by retrospective clinical chart reviews of patients hospitalized in the study center between 2017 and Dec.2020 and fulfilling the same clinical and radiological inclusion criteria in whom 12-month follow-up (including mRS, NIHSS, BI, EQ-5D-5L) could be obtained.

Being tested
Cerebrolysin
Keywords
acute ischemic stroke, effective recanalization, neuroprotection, cerebrolysin
Medical subject headings
Ischemic Stroke, Stroke

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CerebrolysinDrug

    neuroprotection treatment

Study groups in NCT04904341
Study groupRoleWhat they receive
activeExperimentalThe first Cerebrolysin infusion (30 ml mixed with 250 mL of saline) is intended to be initiated as soon as possible after successful recanalization is achieved and within 8h of AIS stroke onset. Cerebrolysin treatment will be continued (30 ml/d) once daily until day 21 (first cycle). The patients will receive a second cycle of treatment (30 ml/d for 21 days given in the Outpatient Department or Neurorehabilitation Clinic) from day 69 to 90 (± 3 days).
Receives: Drug: Cerebrolysin
historical controlNo interventionHistorical data will be obtained by retrospective clinical chart reviews of patients hospitalized in the study center between 2017 and Dec.2020 and fulfilling the same clinical and radiological inclusion criteria in whom 12-month follow-up (including mRS, NIHSS, BI, EQ-5D-5L) could be obtained.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Favorable functional outcome

    proportion of patients who achieve functional independence (defined as 0 to 2 on the Modified Rankin Scale [mRS]; range 0 to 6, with higher scores indicating greater disability) at day 7, 30 days, 90 days and 12 months following stroke onset

    Measured: 7 days - 12 months

Secondary outcomes (7)
  1. Distribution of the modified Rankin Scale (mRS)

    the minimum and maximum values of mRS are 0 and 6, respectively; higher mRS mean a worse outcome

    Measured: 7 days - 12 months or last rating

  2. Proportion of National Institute of Health Stroke scale (NIHSS) 0-2

    the minimum and maximum values of NIHSS are 42 and 0, respectively; higher NIHSS mean a worse outcome,

    Measured: 7 Days, 30 Days, 90 Days

  3. Proportion of death

    death due to any cause

    Measured: 12 months

  4. Proportion of symptomatic intracranial hemorrhage (sICH)

    sICH was defined as 4 or more increase in NIHSS caused by hemorrhage

    Measured: 24 hours

  5. Final infarct volume (mL)

    Final infarct volume according to follow-up CT

    Measured: 30 Days

  6. Penumbral salvage (mL)

    Penumbral salvage will be assessed by subtracting final infarct volume from baseline penumbral volume

    Measured: 24 hours and 30 Days

  7. Infarct growth (mL)

    Infarct growth will be determined by subtracting the ischemic core on acute perfusion imaging from the final infarct volume

    Measured: 24 hours and 30 Days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 May 2021
  2. Study start1 Jan 2021
  3. Primary completion31 Dec 2023 (estimated)
  4. Study completion31 Dec 2024 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Model description
A single centre, prospective, open-label, single-arm study of consecutive 50 patients who will be treated with MT in the reference centre according to local standards and additional Cerebrolysin compared to 50 historical controls treated with MT alone - matched for age, clinical severity, occlusion location, baseline perfusion lesion volume, onset to reperfusion and use of iv rt-PA prior to MT
Masking
None (open label)
Enrolment
50 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04904341
Sponsor's protocol ID
0000000589
Status last verified
Aug 2022
First submitted
18 May 2021
Last updated
24 Aug 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Staszewski J, Debiec A, Strilciuc S, Gniadek-Olejniczak K, Piusinska-Macoch R, Balo D, Harston G, Stepien A, Brzozowski K, Ziecina P, Narloch J, Wierzbicki M, Piasecki P. Efficacy of Cerebrolysin Treatment as an Add-On Therapy to Mechanical Thrombectomy in Patients with Acute Ischemic Stroke Due to Large Vessel Occlusion in Anterior Circulation: Results of a 3-Month Follow-up of a Prospective, Open Label, Single-Center Study. Transl Stroke Res. 2025 Dec;16(6):1931-1946. doi: 10.1007/s12975-025-01355-z. Epub 2025 May 6.

    PubMed 40325343

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Cerebrolysin in people with Stroke, Ischemic and Stroke, Acute, run by Military Institute od Medicine National Research Institute at 1 site in Poland.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 24 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Poland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Jacek Staszewski, MD, PhD (+48261816445, jstaszewski@wim.mil.pl), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Favorable functional outcome (time frame: 7 days - 12 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04904341, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Aug 2022.

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