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Study · Randomized controlled trial · n = 238 · 2023

12 results

Heterogeneous treatment effects of Cerebrolysin as an early add-on to reperfusion therapy: post hoc analysis of the CEREHETIS trial.

Kalinin MN, Khasanova DR

Frontiers in pharmacology5 Jan 2024Cited by 8 (Europe PMC)

PMID38249342 (opens in a new tab)PMCIDPMC10796496 (opens in a new tab)DOI10.3389/fphar.2023.1288718 (opens in a new tab)PepBankPUB-38249342
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Summary

Background: There has been intensive research into enhancing the effects of reperfusion therapy to mitigate hemorrhagic transformation (HT) in stroke patients. Using neuroprotective agents alongside intravenous thrombolysis (IVT) appears a promising approach. Cerebrolysin is one of the candidates since it consists of neuropeptides mimicking the action of neurotrophic factors on brain protection and repair. Objectives: We looked at treatment effects of Cerebrolysin as an early add-on to IVT in stroke patients with varying HT risk. Methods: It was post hoc analysis of the CEREHETIS trial (ISRCTN87656744). Patients with middle cerebral artery infarction (n = 238) were selected from the intention-to-treat population. To stratify participants according to their HT risk, the DRAGON, SEDAN and HTI scores were computed for each eligible subject using on-admission data. The study endpoints were any and symptomatic HT, and functional outcome measured with the modified Rankin Scale (mRS) on day 90. Favorable functional outcome (FFO) was defined as an mRS ≤2. The performance of each stratification tool was estimated with regression approaches. Heterogeneous treatment effect analysis was conducted using techniques of meta-analysis and the matching-smoothing method. Results: The HTI score outperformed other tools in terms of HT risk stratification. Heterogeneity of Cerebrolysin treatment effects was moderate (I2, 35.8%-56.7%; H2, 1.56-2.31) and mild (I2, 10.9%; H2, 1.12) for symptomatic and any HT, respectively. A significant positive impact of Cerebrolysin on HT and functional outcome was observed in the moderate (HTI = 1) and high (HTI ≥2) HT risk patients, but it was neutral in those with the low (HTI = 0) risk. In particular, there was a steady decline in the rate of symptomatic (HTI = 0 vs. HTI = 4: by 4.3%, p = 0.077 vs. 21.1%, p < 0.001) and any HT (HTI = 0 vs. HTI = 4: by 1.2%, p = 0.737 vs. 32.7%, p < 0.001). Likewise, an mRS score reduction (HTI = 0 vs. HTI = 4: by 1.8%, p = 0.903 vs. 126%, p < 0.001) with a reciprocal increase of the fraction of FFO patients (HTI = 0 vs. HTI = 4: by 1.2% p = 0.757 vs. 35.5%, p < 0.001) was found. Conclusion: Clinically meaningful heterogeneity of Cerebrolysin treatment effects on HT and functional outcome was established in stroke patients. The beneficial effects were significant in those whose estimated on-admission HT risk was either moderate or high.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study12

12 results from studies that gave the peptide. 12 results from people.

  1. 01HumanRandomized controlled trialOther

    In stroke patients receiving intravenous thrombolysis, Cerebrolysin effects on symptomatic hemorrhagic transformation showed moderate heterogeneity.

    In plain wordsIn stroke patients receiving thrombolysis, Cerebrolysin effects on symptomatic bleeding showed moderate variation across risk groups.

    Peptide
    Cerebrolysin
    Outcome
    Not applicableSymptomatic hemorrhagic transformation effect heterogeneity
    Study

    n = 238

    Outcome group
    Neuroprotection · Nervous system and cognition
    Studied dose
    Dose not stated

    Measurements

    I2
    35.8 to 56.7%
    symptomatic HT
    H2
    1.56 to 2.31
    symptomatic HT

    Source sentences

    Summary
    Heterogeneity of Cerebrolysin treatment effects was moderate (I2, 35.8%-56.7%; H2, 1.56-2.31) and mild (I2, 10.9%; H2, 1.12) for symptomatic and any HT, respectively.
    3 context sentences
    Summary · context
    It was post hoc analysis of the CEREHETIS trial (ISRCTN87656744).
    Summary · context
    The study endpoints were any and symptomatic HT, and functional outcome measured with the modified Rankin Scale (mRS) on day 90.
    Summary · context
    Favorable functional outcome (FFO) was defined as an mRS ≤2.
  2. 02HumanRandomized controlled trialOther

    In stroke patients receiving intravenous thrombolysis, Cerebrolysin effects on any hemorrhagic transformation showed mild heterogeneity.

    In plain wordsIn stroke patients receiving thrombolysis, Cerebrolysin effects on any bleeding showed mild variation across risk groups.

    Peptide
    Cerebrolysin
    Outcome
    Not applicableAny hemorrhagic transformation effect heterogeneity
    Study

    n = 238

    Outcome group
    Neuroprotection · Nervous system and cognition
    Studied dose
    Dose not stated

    Measurements

    I2
    10.9%
    any HT
    H2
    1.12
    any HT

    Source sentences

    Summary
    Heterogeneity of Cerebrolysin treatment effects was moderate (I2, 35.8%-56.7%; H2, 1.56-2.31) and mild (I2, 10.9%; H2, 1.12) for symptomatic and any HT, respectively.
    3 context sentences
    Summary · context
    It was post hoc analysis of the CEREHETIS trial (ISRCTN87656744).
    Summary · context
    The study endpoints were any and symptomatic HT, and functional outcome measured with the modified Rankin Scale (mRS) on day 90.
    Summary · context
    Favorable functional outcome (FFO) was defined as an mRS ≤2.
  3. 03HumanRandomized controlled trialEfficacy outcome

    In stroke patients with moderate or high HT risk (HTI = 1 or HTI >=2), Cerebrolysin added to intravenous thrombolysis had a significant positive effect on hemorrhagic transformation.

    In plain wordsIn stroke patients at moderate or high bleeding risk, added Cerebrolysin had a significant positive effect on brain bleeding after thrombolysis.

    Peptide
    Cerebrolysin
    Outcome
    DecreaseHemorrhagic transformation in moderate- and high-risk patients
    Study

    n: not reported in source

    Outcome group
    Neuroprotection · Nervous system and cognition
    Studied dose
    Dose not stated

    Source sentences

    Summary
    A significant positive impact of Cerebrolysin on HT and functional outcome was observed in the moderate (HTI = 1) and high (HTI ≥2) HT risk patients, but it was neutral in those with the low (HTI = 0) risk.
    3 context sentences
    Summary · context
    It was post hoc analysis of the CEREHETIS trial (ISRCTN87656744).
    Summary · context
    The study endpoints were any and symptomatic HT, and functional outcome measured with the modified Rankin Scale (mRS) on day 90.
    Summary · context
    Favorable functional outcome (FFO) was defined as an mRS ≤2.
  4. 04HumanRandomized controlled trialEfficacy outcome

    In stroke patients with moderate or high HT risk (HTI = 1 or HTI >=2), Cerebrolysin added to intravenous thrombolysis had a significant positive effect on functional outcome.

    In plain wordsIn stroke patients at moderate or high bleeding risk, added Cerebrolysin had a significant positive effect on function after thrombolysis.

    Peptide
    Cerebrolysin
    Outcome
    IncreaseFunctional outcome in moderate- and high-risk patients
    Study

    n: not reported in source

    Outcome group
    Exercise and physical function · Nervous system and cognition
    Studied dose
    Dose not stated

    Source sentences

    Summary
    A significant positive impact of Cerebrolysin on HT and functional outcome was observed in the moderate (HTI = 1) and high (HTI ≥2) HT risk patients, but it was neutral in those with the low (HTI = 0) risk.
    3 context sentences
    Summary · context
    It was post hoc analysis of the CEREHETIS trial (ISRCTN87656744).
    Summary · context
    The study endpoints were any and symptomatic HT, and functional outcome measured with the modified Rankin Scale (mRS) on day 90.
    Summary · context
    Favorable functional outcome (FFO) was defined as an mRS ≤2.
  5. 05HumanRandomized controlled trialEfficacy outcome

    In stroke patients with HTI = 0, the symptomatic hemorrhagic transformation reduction with Cerebrolysin was not statistically significant.

    In plain wordsIn stroke patients with HTI = 0, added Cerebrolysin did not significantly reduce symptomatic bleeding.

    Peptide
    Cerebrolysin
    Outcome
    No significant changeSymptomatic hemorrhagic transformation at HTI zero
    Study

    n: not reported in source

    Outcome group
    Neuroprotection · Nervous system and cognition
    Studied dose
    Dose not stated

    Measurements

    Rate reduction
    4.3%
    HTI = 0
    P value for Cerebrolysin treatment effect on symptomatic hemorrhagic transformation
    0.077
    Cerebrolysin added to intravenous thrombolysis versus control; HTI = 0

    Source sentences

    Summary
    In particular, there was a steady decline in the rate of symptomatic (HTI = 0 vs. HTI = 4: by 4.3%, p = 0.077 vs. 21.1%, p < 0.001)
    3 context sentences
    Summary · context
    It was post hoc analysis of the CEREHETIS trial (ISRCTN87656744).
    Summary · context
    The study endpoints were any and symptomatic HT, and functional outcome measured with the modified Rankin Scale (mRS) on day 90.
    Summary · context
    Favorable functional outcome (FFO) was defined as an mRS ≤2.
  6. 06HumanRandomized controlled trialEfficacy outcome

    In stroke patients with HTI = 4, Cerebrolysin significantly reduced symptomatic hemorrhagic transformation.

    In plain wordsIn stroke patients with HTI = 4, added Cerebrolysin significantly reduced symptomatic bleeding.

    Peptide
    Cerebrolysin
    Outcome
    DecreaseSymptomatic hemorrhagic transformation at HTI four
    Study

    n: not reported in source

    Outcome group
    Neuroprotection · Nervous system and cognition
    Studied dose
    Dose not stated

    Measurements

    Rate reduction
    21.1%
    HTI = 4
    P value for Cerebrolysin treatment effect on symptomatic hemorrhagic transformation
    < 0.001
    Cerebrolysin added to intravenous thrombolysis versus control; HTI = 4

    Source sentences

    Summary
    In particular, there was a steady decline in the rate of symptomatic (HTI = 0 vs. HTI = 4: by 4.3%, p = 0.077 vs. 21.1%, p < 0.001)
    3 context sentences
    Summary · context
    It was post hoc analysis of the CEREHETIS trial (ISRCTN87656744).
    Summary · context
    The study endpoints were any and symptomatic HT, and functional outcome measured with the modified Rankin Scale (mRS) on day 90.
    Summary · context
    Favorable functional outcome (FFO) was defined as an mRS ≤2.
  7. 07HumanRandomized controlled trialEfficacy outcome

    In stroke patients with HTI = 0, the reduction in any hemorrhagic transformation with Cerebrolysin was not statistically significant.

    In plain wordsIn stroke patients with HTI = 0, added Cerebrolysin did not significantly reduce any bleeding.

    Peptide
    Cerebrolysin
    Outcome
    No significant changeAny hemorrhagic transformation at HTI zero
    Study

    n: not reported in source

    Outcome group
    Neuroprotection · Nervous system and cognition
    Studied dose
    Dose not stated

    Measurements

    Rate reduction
    1.2%
    HTI = 0
    P value for Cerebrolysin treatment effect on any hemorrhagic transformation
    0.737
    Cerebrolysin added to intravenous thrombolysis versus control; HTI = 0

    Source sentences

    Summary
    and any HT (HTI = 0 vs. HTI = 4: by 1.2%, p = 0.737 vs. 32.7%, p < 0.001).
    3 context sentences
    Summary · context
    It was post hoc analysis of the CEREHETIS trial (ISRCTN87656744).
    Summary · context
    The study endpoints were any and symptomatic HT, and functional outcome measured with the modified Rankin Scale (mRS) on day 90.
    Summary · context
    Favorable functional outcome (FFO) was defined as an mRS ≤2.
  8. 08HumanRandomized controlled trialEfficacy outcome

    In stroke patients with HTI = 4, Cerebrolysin significantly reduced any hemorrhagic transformation.

    In plain wordsIn stroke patients with HTI = 4, added Cerebrolysin significantly reduced any bleeding.

    Peptide
    Cerebrolysin
    Outcome
    DecreaseAny hemorrhagic transformation at HTI four
    Study

    n: not reported in source

    Outcome group
    Neuroprotection · Nervous system and cognition
    Studied dose
    Dose not stated

    Measurements

    Rate reduction
    32.7%
    HTI = 4
    P value for Cerebrolysin treatment effect on any hemorrhagic transformation
    < 0.001
    Cerebrolysin added to intravenous thrombolysis versus control; HTI = 4

    Source sentences

    Summary
    and any HT (HTI = 0 vs. HTI = 4: by 1.2%, p = 0.737 vs. 32.7%, p < 0.001).
    3 context sentences
    Summary · context
    It was post hoc analysis of the CEREHETIS trial (ISRCTN87656744).
    Summary · context
    The study endpoints were any and symptomatic HT, and functional outcome measured with the modified Rankin Scale (mRS) on day 90.
    Summary · context
    Favorable functional outcome (FFO) was defined as an mRS ≤2.
  9. 09HumanRandomized controlled trialEfficacy outcome

    In stroke patients with HTI = 0, the modified Rankin Scale reduction with Cerebrolysin was not statistically significant.

    In plain wordsIn stroke patients with HTI = 0, added Cerebrolysin did not significantly reduce disability scores.

    Peptide
    Cerebrolysin
    Outcome
    No significant changeModified Rankin Scale at HTI zero
    Study

    n: not reported in source

    Outcome group
    Exercise and physical function · Nervous system and cognition
    Studied dose
    Dose not stated

    Measurements

    mRS reduction
    1.8%
    HTI = 0
    P value for Cerebrolysin treatment effect on modified Rankin Scale score on day 90
    0.903
    Cerebrolysin added to intravenous thrombolysis versus control; HTI = 0

    Source sentences

    Summary
    Likewise, an mRS score reduction (HTI = 0 vs. HTI = 4: by 1.8%, p = 0.903 vs. 126%, p < 0.001)
    3 context sentences
    Summary · context
    It was post hoc analysis of the CEREHETIS trial (ISRCTN87656744).
    Summary · context
    The study endpoints were any and symptomatic HT, and functional outcome measured with the modified Rankin Scale (mRS) on day 90.
    Summary · context
    Favorable functional outcome (FFO) was defined as an mRS ≤2.
  10. 10HumanRandomized controlled trialEfficacy outcome

    In stroke patients with HTI = 4, Cerebrolysin significantly reduced modified Rankin Scale scores.

    In plain wordsIn stroke patients with HTI = 4, added Cerebrolysin significantly reduced disability scores.

    Peptide
    Cerebrolysin
    Outcome
    DecreaseModified Rankin Scale at HTI four
    Study

    n: not reported in source

    Outcome group
    Exercise and physical function · Nervous system and cognition
    Studied dose
    Dose not stated

    Measurements

    mRS reduction
    126%
    HTI = 4
    P value for Cerebrolysin treatment effect on modified Rankin Scale score on day 90
    < 0.001
    Cerebrolysin added to intravenous thrombolysis versus control; HTI = 4

    Source sentences

    Summary
    Likewise, an mRS score reduction (HTI = 0 vs. HTI = 4: by 1.8%, p = 0.903 vs. 126%, p < 0.001)
    3 context sentences
    Summary · context
    It was post hoc analysis of the CEREHETIS trial (ISRCTN87656744).
    Summary · context
    The study endpoints were any and symptomatic HT, and functional outcome measured with the modified Rankin Scale (mRS) on day 90.
    Summary · context
    Favorable functional outcome (FFO) was defined as an mRS ≤2.
  11. 11HumanRandomized controlled trialEfficacy outcome

    In stroke patients with HTI = 0, the increase in favorable functional outcomes with Cerebrolysin was not statistically significant.

    In plain wordsIn stroke patients with HTI = 0, added Cerebrolysin did not significantly increase favorable functional outcomes.

    Peptide
    Cerebrolysin
    Outcome
    No significant changeFavorable functional outcome at HTI zero
    Study

    n: not reported in source

    Outcome group
    Exercise and physical function · Nervous system and cognition
    Studied dose
    Dose not stated

    Measurements

    FFO increase
    1.2%
    HTI = 0
    P value for Cerebrolysin treatment effect on fraction of favorable functional outcome patients on day 90
    0.757
    Cerebrolysin added to intravenous thrombolysis versus control; HTI = 0

    Source sentences

    Summary
    with a reciprocal increase of the fraction of FFO patients (HTI = 0 vs. HTI = 4: by 1.2% p = 0.757 vs. 35.5%, p < 0.001) was found.
    3 context sentences
    Summary · context
    It was post hoc analysis of the CEREHETIS trial (ISRCTN87656744).
    Summary · context
    The study endpoints were any and symptomatic HT, and functional outcome measured with the modified Rankin Scale (mRS) on day 90.
    Summary · context
    Favorable functional outcome (FFO) was defined as an mRS ≤2.
  12. 12HumanObservational studyEfficacy outcome

    In stroke patients with HTI = 4, Cerebrolysin significantly increased the fraction with favorable functional outcomes.

    In plain wordsIn stroke patients with HTI = 4, added Cerebrolysin significantly increased favorable functional outcomes.

    Peptide
    Cerebrolysin
    Outcome
    IncreaseFavorable functional outcome at HTI four
    Study

    n: not reported in source

    Outcome group
    Exercise and physical function · Nervous system and cognition
    Studied dose
    Dose not stated

    Measurements

    FFO increase
    35.5%
    HTI = 4
    P value for Cerebrolysin treatment effect on fraction of favorable functional outcome patients on day 90
    < 0.001
    Cerebrolysin added to intravenous thrombolysis versus control; HTI = 4

    Source sentences

    Summary
    with a reciprocal increase of the fraction of FFO patients (HTI = 0 vs. HTI = 4: by 1.2% p = 0.757 vs. 35.5%, p < 0.001) was found.
    3 context sentences
    Summary · context
    It was post hoc analysis of the CEREHETIS trial (ISRCTN87656744).
    Summary · context
    The study endpoints were any and symptomatic HT, and functional outcome measured with the modified Rankin Scale (mRS) on day 90.
    Summary · context
    Favorable functional outcome (FFO) was defined as an mRS ≤2.

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    14 Oct 2026, 05:02 UTC

    Study results updated

  2. Version 1

    14 Oct 2026, 01:46 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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