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Safety and efficacy of Cerebrolysin in acute brain injury and neurorecovery: CAPTAIN I—a randomized, placebo-controlled, double-blind, Asian-Pacific trial

  • W. Poon
  • C. Matula
  • P. E. Vos
  • D. F. MuresanuEmail author
  • N. von Steinbüchel
  • K. von Wild
  • V. Hömberg
  • E. Wang
  • T. M. C. Lee
  • S. Strilciuc
  • J. C. Vester
Original Article

Abstract

Objective

To evaluate the safety and efficacy of Cerebrolysin as an add-on therapy to local standard treatment protocol in patients after moderate-to-severe traumatic brain injury.

Methods

The patients received the study medication in addition to standard care (50 mL of Cerebrolysin or physiological saline solution daily for 10 days, followed by two additional treatment cycles with 10 mL daily for 10 days) in a prospective, randomized, double-blind, placebo-controlled, parallel-group, multi-centre phase IIIb/IV trial. The primary endpoint was a multidimensional ensemble of 14 outcome scales pooled to be analyzed by means of the multivariate, correlation-sensitive Wei-Lachin procedure.

Results

In 46 enrolled TBI patients (Cerebrolysin 22, placebo 24), three single outcomes showed stand-alone statistically significant superiority of Cerebrolysin [Stroop Word/Dots Interference (p = 0.0415, Mann–Whitney(MW) = 0.6816, 95% CI 0.51–0.86); Color Trails Tests 1 and 2 (p = 0.0223/0.0170, MW = 0.72/0.73, 95% CI 0.53–0.90/0.54–0.91), both effect sizes lying above the benchmark for “large” superiority (MW > 0.71)]. While for the primary multivariate ensemble, statistical significance was just missed in the intention-to-treat population (pWei-Lachin < 0.1, MWcombined = 0.63, 95% CI 0.48–0.77, derived standardized mean difference (SMD) 0.45, 95% CI −0.07 to 1.04, derived OR 2.1, 95% CI 0.89–5.95), the per-protocol analysis showed a statistical significant superiority of Cerebrolysin (pWei-Lachin = 0.0240, MWcombined = 0.69, 95% CI 0.53 to 0.85, derived SMD 0.69, 95% CI 0.09 to 1.47, derived OR 3.2, 95% CI 1.16 to 12.8), with effect sizes of six single outcomes lying above the benchmark for “large” superiority. Safety aspects were comparable to placebo.

Conclusion

Our trial suggests beneficial effects of Cerebrolysin on outcome after TBI. Results should be confirmed by a larger RCT with a comparable multidimensional approach.

Keywords

Traumatic brain injury Cerebrolysin Multidimensional approach Wei-Lachin pooling 

Notes

Funding

This study was funded by Ever Neuro Pharma GmbH.

Compliance with ethical standards

Ethical approval

All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and/or national research committees of all participating countries and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Conflict of interest

The authors of this trial disclose a research grant from Ever Neuro Pharma GmbH, along with no other relevant conflict of interest.

Supplementary material

10072_2019_4053_MOESM1_ESM.docx (20 kb)
ESM 1 (DOCX 19 kb)

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Copyright information

© Fondazione Società Italiana di Neurologia 2019

Authors and Affiliations

  • W. Poon
    • 1
  • C. Matula
    • 2
  • P. E. Vos
    • 3
  • D. F. Muresanu
    • 4
    • 5
    Email author
  • N. von Steinbüchel
    • 6
  • K. von Wild
    • 7
  • V. Hömberg
    • 8
  • E. Wang
    • 9
  • T. M. C. Lee
    • 10
  • S. Strilciuc
    • 4
    • 5
  • J. C. Vester
    • 11
  1. 1.Division of Neurosurgery, Prince of Wales HospitalThe Chinese University of Hong KongShatinHong Kong, China
  2. 2.Department of NeurosurgeryMedical University of ViennaViennaAustria
  3. 3.Department of NeurologySlingeland HospitalDoetinchemThe Netherlands
  4. 4.Department of Clinical Neurosciences“Iuliu Hatieganu” University of Medicine and PharmacyCluj-NapocaRomania
  5. 5.RoNeuro Institute for Neurological Research and DiagnosticCluj-NapocaRomania
  6. 6.Institute of Medical Psychology and Medical SociologyUniversity Medical Centre GöttingenGöttingenGermany
  7. 7.Medical FacultyWestphalia Wilhelm’s UniversityMünsterGermany
  8. 8.Department of NeurologySRH Gesundheitszentrum Bad Wimpfen GmbHBad WimpfenGermany
  9. 9.Department of NeurosurgeryNational Neuroscience InstituteSingaporeSingapore
  10. 10.State Key Laboratory of Brain and Cognitive Sciences and Laboratory of NeuropsychologyThe University of Hong KongPokfulamHong Kong, China
  11. 11.Department of Biometry and Clinical Researchidv Data Analysis and Study PlanningKraillingGermany

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