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

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.

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Change history

  • 06 January 2020

    The above article was published online with incorrect abbreviations in Figures��2 and 3 last sentence of the legend. HDA should be corrected to HADS.

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Funding

This study was funded by Ever Neuro Pharma GmbH.

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Correspondence to D. F. Muresanu.

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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.

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

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The original version of this article was revised: The above article was published online with incorrect abbreviations in Figures 2 and 3 last sentence of the legend. HDA should be corrected to HADS. The correct presentation has been corrected below: “HDA-3LPCF, HADS: Anxiety Sumscore; HDD-3LPCF, HADS: Depression Sumscore; Visit No. 3 = Day 30

E. Wang is deceased

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Poon, W., Matula, C., Vos, P.E. et al. Safety and efficacy of Cerebrolysin in acute brain injury and neurorecovery: CAPTAIN I—a randomized, placebo-controlled, double-blind, Asian-Pacific trial. Neurol Sci 41, 281–293 (2020). https://doi.org/10.1007/s10072-019-04053-5

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Keywords

  • Traumatic brain injury
  • Cerebrolysin
  • Multidimensional approach
  • Wei-Lachin pooling