title: Cerebrolysin and Recovery After Stroke (CARS): A Randomized, Placebo-Controlled, Double-Blind, Multicenter Trial.
abstract: OBJECTIVE
  The aim of this trial was to investigate whether stroke patients who receive Cerebrolysin show improved motor function in the upper extremities at day 90 compared with patients who receive a placebo.
  
  
  METHODS
  This study was a prospective, randomized, double-blind, placebo-controlled, multicenter, parallel-group study. Patients were treated with Cerebrolysin (30 mL/d) or a placebo (saline) once daily for 21 days, beginning at 24 to 72 hours after stroke onset. The patients also participated in a standardized rehabilitation program for 21 days that was initiated within 72 hours after stroke onset. The primary end point was the Action Research Arm Test score on day 90.
  
  
  RESULTS
  The nonparametric effect size on the Action Research Arm Test score on day 90 indicated a large superiority of Cerebrolysin compared with the placebo (Mann-Whitney estimator, 0.71; 95% confidence interval, 0.63-0.79; P<0.0001). The multivariate effect size on global status, as assessed using 12 different outcome scales, indicated a small-to-medium superiority of Cerebrolysin (Mann-Whitney estimator, 0.62; 95% confidence interval, 0.58-0.65; P<0.0001). The rate of premature discontinuation was <5% (3.8%). Cerebrolysin was safe and well tolerated.
  
  
  CONCLUSIONS
  Cerebrolysin had a beneficial effect on function and global outcome in early rehabilitation patients after stroke. Its safety was comparable with that of the placebo, suggesting a favorable benefit/risk ratio. Because this study was exploratory and had a relatively small sample size, the results should be confirmed in a large-scale, randomized clinical trial.
  
  
  BACKGROUND
  URL: http://www.clinicaltrialsregister.eu. Unique identifier: 2007-000870-21.
authors.affiliation: From the Department of Clinical Neurosciences, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania (D.F.M.); Max Planck Institute for Metabolism Research, Cologne, Germany (W.-D.H.); Department of Neurology, SHR Gesundheitszentrum Bad Wimpfen GmbH, Bad Wimpfen, Germany (V.H.); Department of Neurology, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania (O.B.); Department of Neurology, "Grigore T. Popa" University of Medicine and Pharmacy, Iasi, Romania (C.D.P.); Department of Biometry and Clinical Research, IDV Data Analysis and Study Planning, Krailling, Germany (J.C.V., V.W.R.); Department of Clinical Research, EVER Neuro Pharma GmbH, Unterach, Austria (E.D., D.M., H.M.); Department of Neurology, Neurosurgery and Genetics, Russian National Research Medical University, Moscow City Hospital No. 8 for Neuropsychiatry, Moscow, Russia (A.G.); and "RoNeuro" Institute for Neurological Research and Diagnostic, Cluj-Napoca, Romania (D.F.M.). dafinm@ssnn.ro.
authors.forename: Dafin F
authors.initials: DF
authors.lastname: Muresanu
authors.affiliation: From the Department of Clinical Neurosciences, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania (D.F.M.); Max Planck Institute for Metabolism Research, Cologne, Germany (W.-D.H.); Department of Neurology, SHR Gesundheitszentrum Bad Wimpfen GmbH, Bad Wimpfen, Germany (V.H.); Department of Neurology, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania (O.B.); Department of Neurology, "Grigore T. Popa" University of Medicine and Pharmacy, Iasi, Romania (C.D.P.); Department of Biometry and Clinical Research, IDV Data Analysis and Study Planning, Krailling, Germany (J.C.V., V.W.R.); Department of Clinical Research, EVER Neuro Pharma GmbH, Unterach, Austria (E.D., D.M., H.M.); Department of Neurology, Neurosurgery and Genetics, Russian National Research Medical University, Moscow City Hospital No. 8 for Neuropsychiatry, Moscow, Russia (A.G.); and "RoNeuro" Institute for Neurological Research and Diagnostic, Cluj-Napoca, Romania (D.F.M.).
authors.forename: Wolf-Dieter
authors.initials: WD
authors.lastname: Heiss
authors.affiliation: From the Department of Clinical Neurosciences, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania (D.F.M.); Max Planck Institute for Metabolism Research, Cologne, Germany (W.-D.H.); Department of Neurology, SHR Gesundheitszentrum Bad Wimpfen GmbH, Bad Wimpfen, Germany (V.H.); Department of Neurology, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania (O.B.); Department of Neurology, "Grigore T. Popa" University of Medicine and Pharmacy, Iasi, Romania (C.D.P.); Department of Biometry and Clinical Research, IDV Data Analysis and Study Planning, Krailling, Germany (J.C.V., V.W.R.); Department of Clinical Research, EVER Neuro Pharma GmbH, Unterach, Austria (E.D., D.M., H.M.); Department of Neurology, Neurosurgery and Genetics, Russian National Research Medical University, Moscow City Hospital No. 8 for Neuropsychiatry, Moscow, Russia (A.G.); and "RoNeuro" Institute for Neurological Research and Diagnostic, Cluj-Napoca, Romania (D.F.M.).
authors.forename: Volker
authors.initials: V
authors.lastname: Hoemberg
authors.affiliation: From the Department of Clinical Neurosciences, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania (D.F.M.); Max Planck Institute for Metabolism Research, Cologne, Germany (W.-D.H.); Department of Neurology, SHR Gesundheitszentrum Bad Wimpfen GmbH, Bad Wimpfen, Germany (V.H.); Department of Neurology, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania (O.B.); Department of Neurology, "Grigore T. Popa" University of Medicine and Pharmacy, Iasi, Romania (C.D.P.); Department of Biometry and Clinical Research, IDV Data Analysis and Study Planning, Krailling, Germany (J.C.V., V.W.R.); Department of Clinical Research, EVER Neuro Pharma GmbH, Unterach, Austria (E.D., D.M., H.M.); Department of Neurology, Neurosurgery and Genetics, Russian National Research Medical University, Moscow City Hospital No. 8 for Neuropsychiatry, Moscow, Russia (A.G.); and "RoNeuro" Institute for Neurological Research and Diagnostic, Cluj-Napoca, Romania (D.F.M.).
authors.forename: Ovidiu
authors.initials: O
authors.lastname: Bajenaru
authors.affiliation: From the Department of Clinical Neurosciences, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania (D.F.M.); Max Planck Institute for Metabolism Research, Cologne, Germany (W.-D.H.); Department of Neurology, SHR Gesundheitszentrum Bad Wimpfen GmbH, Bad Wimpfen, Germany (V.H.); Department of Neurology, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania (O.B.); Department of Neurology, "Grigore T. Popa" University of Medicine and Pharmacy, Iasi, Romania (C.D.P.); Department of Biometry and Clinical Research, IDV Data Analysis and Study Planning, Krailling, Germany (J.C.V., V.W.R.); Department of Clinical Research, EVER Neuro Pharma GmbH, Unterach, Austria (E.D., D.M., H.M.); Department of Neurology, Neurosurgery and Genetics, Russian National Research Medical University, Moscow City Hospital No. 8 for Neuropsychiatry, Moscow, Russia (A.G.); and "RoNeuro" Institute for Neurological Research and Diagnostic, Cluj-Napoca, Romania (D.F.M.).
authors.forename: Cristian Dinu
authors.initials: CD
authors.lastname: Popescu
authors.affiliation: From the Department of Clinical Neurosciences, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania (D.F.M.); Max Planck Institute for Metabolism Research, Cologne, Germany (W.-D.H.); Department of Neurology, SHR Gesundheitszentrum Bad Wimpfen GmbH, Bad Wimpfen, Germany (V.H.); Department of Neurology, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania (O.B.); Department of Neurology, "Grigore T. Popa" University of Medicine and Pharmacy, Iasi, Romania (C.D.P.); Department of Biometry and Clinical Research, IDV Data Analysis and Study Planning, Krailling, Germany (J.C.V., V.W.R.); Department of Clinical Research, EVER Neuro Pharma GmbH, Unterach, Austria (E.D., D.M., H.M.); Department of Neurology, Neurosurgery and Genetics, Russian National Research Medical University, Moscow City Hospital No. 8 for Neuropsychiatry, Moscow, Russia (A.G.); and "RoNeuro" Institute for Neurological Research and Diagnostic, Cluj-Napoca, Romania (D.F.M.).
authors.forename: Johannes C
authors.initials: JC
authors.lastname: Vester
authors.affiliation: From the Department of Clinical Neurosciences, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania (D.F.M.); Max Planck Institute for Metabolism Research, Cologne, Germany (W.-D.H.); Department of Neurology, SHR Gesundheitszentrum Bad Wimpfen GmbH, Bad Wimpfen, Germany (V.H.); Department of Neurology, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania (O.B.); Department of Neurology, "Grigore T. Popa" University of Medicine and Pharmacy, Iasi, Romania (C.D.P.); Department of Biometry and Clinical Research, IDV Data Analysis and Study Planning, Krailling, Germany (J.C.V., V.W.R.); Department of Clinical Research, EVER Neuro Pharma GmbH, Unterach, Austria (E.D., D.M., H.M.); Department of Neurology, Neurosurgery and Genetics, Russian National Research Medical University, Moscow City Hospital No. 8 for Neuropsychiatry, Moscow, Russia (A.G.); and "RoNeuro" Institute for Neurological Research and Diagnostic, Cluj-Napoca, Romania (D.F.M.).
authors.forename: Volker W
authors.initials: VW
authors.lastname: Rahlfs
authors.affiliation: From the Department of Clinical Neurosciences, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania (D.F.M.); Max Planck Institute for Metabolism Research, Cologne, Germany (W.-D.H.); Department of Neurology, SHR Gesundheitszentrum Bad Wimpfen GmbH, Bad Wimpfen, Germany (V.H.); Department of Neurology, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania (O.B.); Department of Neurology, "Grigore T. Popa" University of Medicine and Pharmacy, Iasi, Romania (C.D.P.); Department of Biometry and Clinical Research, IDV Data Analysis and Study Planning, Krailling, Germany (J.C.V., V.W.R.); Department of Clinical Research, EVER Neuro Pharma GmbH, Unterach, Austria (E.D., D.M., H.M.); Department of Neurology, Neurosurgery and Genetics, Russian National Research Medical University, Moscow City Hospital No. 8 for Neuropsychiatry, Moscow, Russia (A.G.); and "RoNeuro" Institute for Neurological Research and Diagnostic, Cluj-Napoca, Romania (D.F.M.).
authors.forename: Edith
authors.initials: E
authors.lastname: Doppler
authors.affiliation: From the Department of Clinical Neurosciences, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania (D.F.M.); Max Planck Institute for Metabolism Research, Cologne, Germany (W.-D.H.); Department of Neurology, SHR Gesundheitszentrum Bad Wimpfen GmbH, Bad Wimpfen, Germany (V.H.); Department of Neurology, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania (O.B.); Department of Neurology, "Grigore T. Popa" University of Medicine and Pharmacy, Iasi, Romania (C.D.P.); Department of Biometry and Clinical Research, IDV Data Analysis and Study Planning, Krailling, Germany (J.C.V., V.W.R.); Department of Clinical Research, EVER Neuro Pharma GmbH, Unterach, Austria (E.D., D.M., H.M.); Department of Neurology, Neurosurgery and Genetics, Russian National Research Medical University, Moscow City Hospital No. 8 for Neuropsychiatry, Moscow, Russia (A.G.); and "RoNeuro" Institute for Neurological Research and Diagnostic, Cluj-Napoca, Romania (D.F.M.).
authors.forename: Dieter
authors.initials: D
authors.lastname: Meier
authors.affiliation: From the Department of Clinical Neurosciences, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania (D.F.M.); Max Planck Institute for Metabolism Research, Cologne, Germany (W.-D.H.); Department of Neurology, SHR Gesundheitszentrum Bad Wimpfen GmbH, Bad Wimpfen, Germany (V.H.); Department of Neurology, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania (O.B.); Department of Neurology, "Grigore T. Popa" University of Medicine and Pharmacy, Iasi, Romania (C.D.P.); Department of Biometry and Clinical Research, IDV Data Analysis and Study Planning, Krailling, Germany (J.C.V., V.W.R.); Department of Clinical Research, EVER Neuro Pharma GmbH, Unterach, Austria (E.D., D.M., H.M.); Department of Neurology, Neurosurgery and Genetics, Russian National Research Medical University, Moscow City Hospital No. 8 for Neuropsychiatry, Moscow, Russia (A.G.); and "RoNeuro" Institute for Neurological Research and Diagnostic, Cluj-Napoca, Romania (D.F.M.).
authors.forename: Herbert
authors.initials: H
authors.lastname: Moessler
authors.affiliation: From the Department of Clinical Neurosciences, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania (D.F.M.); Max Planck Institute for Metabolism Research, Cologne, Germany (W.-D.H.); Department of Neurology, SHR Gesundheitszentrum Bad Wimpfen GmbH, Bad Wimpfen, Germany (V.H.); Department of Neurology, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania (O.B.); Department of Neurology, "Grigore T. Popa" University of Medicine and Pharmacy, Iasi, Romania (C.D.P.); Department of Biometry and Clinical Research, IDV Data Analysis and Study Planning, Krailling, Germany (J.C.V., V.W.R.); Department of Clinical Research, EVER Neuro Pharma GmbH, Unterach, Austria (E.D., D.M., H.M.); Department of Neurology, Neurosurgery and Genetics, Russian National Research Medical University, Moscow City Hospital No. 8 for Neuropsychiatry, Moscow, Russia (A.G.); and "RoNeuro" Institute for Neurological Research and Diagnostic, Cluj-Napoca, Romania (D.F.M.).
authors.forename: Alla
authors.initials: A
authors.lastname: Guekht
mesh_terms: D000368:Aged; D000596:Amino Acids / Q000494:pharmacology / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D011446:Prospective Studies; D020127:Recovery of Function / Q000187:drug effects; D020521:Stroke / Q000175:diagnosis* / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000596:Amino Acids; D018696:Neuroprotective Agents; C006952:cerebrolysin
keywords: Cerebrolysin; randomized, double-blind, placebo-controlled trial; recovery of function; rehabilitation; stroke