Dafin F Muresanu1,2, Stefan Florian3, Volker Hömberg4, Christian Matula5, Nicole von Steinbüchel6, Pieter E Vos7, Klaus von Wild8, Codruta Birle3,9, Ioana Muresanu3,9, Dana Slavoaca3,9, Olivia Verisezan Rosu3,9, Stefan Strilciuc3,9, Johannes Vester10. 1. Department of Neurosciences, "Iuliu Hatieganu", University of Medicine and Pharmacy, No. 43 Victor Babes Street, 400012, Cluj-Napoca, Romania. dafinm@ssnn.ro. 2. RoNeuro Institute for Neurological Research and Diagnostic, Cluj-Napoca, Romania. dafinm@ssnn.ro. 3. Department of Neurosciences, "Iuliu Hatieganu", University of Medicine and Pharmacy, No. 43 Victor Babes Street, 400012, Cluj-Napoca, Romania. 4. Department of Neurology, SRH Gesundheitszentrum Bad Wimpfen GmbH, Bei der alten Saline 2, 74206, Bad Wimpfen, Germany. 5. Department of Neurosurgery, Medical University of Vienna, Vienna, Austria. 6. Institute of Medical Psychology and Medical Sociology, University Medical Centre Göttingen, Göttingen, Germany. 7. Department of Neurology, Slingeland Hospital, Kruisbergseweg 25, 7009 BL, Doetinchem, Netherlands. 8. Medical Faculty, Westphalia Wilhelm's University, Münster, Germany. 9. RoNeuro Institute for Neurological Research and Diagnostic, Cluj-Napoca, Romania. 10. Department of Biometry and Clinical Research, idv Data Analysis and Study Planning, Gauting, Germany.
Abstract
INTRODUCTION: The objective of this trial was to evaluate the efficacy and safety of Cerebrolysin in treating patients after moderate to severe traumatic brain injury (TBI) as an adjunct to standard care protocols. The trial was designed to investigate the clinical effects of Cerebrolysin in the acute (neuroprotective) stage and during early and long-term recovery as part of a neurorestorative strategy. MATERIALS AND METHODS: The study was a phase IIIb/IV single-center, prospective, randomized, double-blind, placebo-controlled clinical trial. Eligible patients with a Glasgow Coma Score (GCS) between 7 and 12 receivedstudy medication (50 ml of Cerebrolysin or physiological saline solution per day for 10 days, followed by two additional treatment cycles with 10 ml per day for 10 days) in addition to standard care. We tested ensembles of efficacy criteria for 90, 30, and 10 days after TBI with a priori ordered hypotheses using a multivariate, directional test, to reflect the global status of patients after TBI. RESULTS: The study enrolled 142 patients, of which 139 underwent formal analysis (mean age = 47.4, mean admission GCS = 10.4, and mean Baseline Prognostic Risk Score = 2.6). The primary endpoint, a multidimensional ensemble of 13 outcome scales, indicated a "small-to-medium"-sized effect in favor of Cerebrolysin, statistically significant at day 90 (MWcombined = 0.59, 95% CI 0.52 to 0.66, P = 0.0119). Safety and tolerability observations were comparable between treatment groups. CONCLUSION: Our trial confirms previous beneficial effects of the multimodal, biological agent Cerebrolysin for overall outcome after moderate to severe TBI, as measured by a multidimensional approach. Study findings must be appraised and aggregated in conjunction with existing literature, as to improve the overall level of insight regarding therapeutic options for TBI patients. The widely used pharmacologic intervention may benefit from a large-scale observational study to map its use and to establish comparative effectiveness in real-world clinical settings.
RCT Entities:
INTRODUCTION: The objective of this trial was to evaluate the efficacy and safety of Cerebrolysin in treating patients after moderate to severe traumatic brain injury (TBI) as an adjunct to standard care protocols. The trial was designed to investigate the clinical effects of Cerebrolysin in the acute (neuroprotective) stage and during early and long-term recovery as part of a neurorestorative strategy. MATERIALS AND METHODS: The study was a phase IIIb/IV single-center, prospective, randomized, double-blind, placebo-controlled clinical trial. Eligible patients with a Glasgow Coma Score (GCS) between 7 and 12 received study medication (50 ml of Cerebrolysin or physiological saline solution per day for 10 days, followed by two additional treatment cycles with 10 ml per day for 10 days) in addition to standard care. We tested ensembles of efficacy criteria for 90, 30, and 10 days after TBI with a priori ordered hypotheses using a multivariate, directional test, to reflect the global status of patients after TBI. RESULTS: The study enrolled 142 patients, of which 139 underwent formal analysis (mean age = 47.4, mean admission GCS = 10.4, and mean Baseline Prognostic Risk Score = 2.6). The primary endpoint, a multidimensional ensemble of 13 outcome scales, indicated a "small-to-medium"-sized effect in favor of Cerebrolysin, statistically significant at day 90 (MWcombined = 0.59, 95% CI 0.52 to 0.66, P = 0.0119). Safety and tolerability observations were comparable between treatment groups. CONCLUSION: Our trial confirms previous beneficial effects of the multimodal, biological agent Cerebrolysin for overall outcome after moderate to severe TBI, as measured by a multidimensional approach. Study findings must be appraised and aggregated in conjunction with existing literature, as to improve the overall level of insight regarding therapeutic options for TBIpatients. The widely used pharmacologic intervention may benefit from a large-scale observational study to map its use and to establish comparative effectiveness in real-world clinical settings.