Cerebrolysin in Patients With Acute Ischemic Stroke in Asia

Wolf-Dieter Heiss; Michael Brainin; Natan M. Bornstein; Jaakko Tuomilehto; Zhen Hong

doi:10.1161/strokeaha.111.628537

journal article Mar 01, 2012

Cerebrolysin in Patients With Acute Ischemic Stroke in Asia

Wolf-Dieter Heiss Michael Brainin

Natan M. Bornstein Jaakko Tuomilehto Zhen Hong

Stroke Vol. 43 No. 3 pp. 630-636 · Ovid Technologies (Wolters Kluwer Health)

View at Publisher Save 10.1161/strokeaha.111.628537

Abstract

Background and Purpose—
Cerebrolysin showed neuroprotective and neurotrophic properties in various preclinical models of ischemia and small clinical trials. The aim of this large double-blind, placebo-controlled randomized clinical trial was to test its efficacy and safety in patients with acute ischemic stroke.

Methods—
Patients with acute ischemic hemispheric stroke were randomized within 12 hours of symptoms onset to active treatment (30 mL Cerebrolysin daily) or placebo (saline solution) given as intravenous infusion for 10 days in addition to aspirin (100 mg daily). The patients were followed up to 90 days. The primary end point was the result of a combined global directional test of modified Rankin Scale, Barthel Index, and National Institutes of Health Stroke Scale. Adverse events were documented to assess safety.

Results—
A total of 1070 patients were enrolled in this study. Five hundred twenty-nine patients were assigned to Cerebrolysin and 541 to placebo. The confirmatory end point showed no significant difference between the treatment groups. When stratified by severity however, a post hoc analysis of National Institutes of Health Stroke Scale and modified Rankin Scale showed a trend in favor of Cerebrolysin in patients with National Institutes of Health Stroke Scale >12 (National Institutes of Health Stroke Scale: OR, 1.27; CI lower bound, 0.97; modified Rankin Scale: OR, 1.27; CI lower bound, 0.90). In this subgroup, the cumulative mortality by 90 days was 20.2% in the placebo and 10.5% in the Cerebrolysin group (hazard ratio, 1.9661; CI lower bound, 1.0013).

Conclusions—
In this study, the confirmatory end point showed neutral results between the treatment groups. However, a favorable outcome trend was seen in the severely affected patients with ischemic stroke treated with Cerebrolysin. This observation should be confirmed by a further clinical trial.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00868283.

Topics

No keywords indexed for this article. Browse by subject →

References

27

[1]

10.1111/j.1368-5031.2006.00873.x

[2]

10.1007/s11940-003-0027-7

[3]

10.1161/01.str.0000072983.64326.53

[4]

10.1161/01.str.32.7.1598

[5]

10.1016/j.neurobiolaging.2006.05.036

[6]

Tatebayashi Y, Lee MH, Li L, Iqbal K, Grundke-Iqbal I . The dentate gyrus neurogenesis: a therapeutic target for Alzheimer's disease. Acta Neuropathol. 2003;105:225–232. 10.1007/s00401-002-0636-3

[7]

10.1080/10298420290007637

[8]

10.1007/s00702-005-0384-3

[9]

10.1007/s00702-005-0302-8

[10]

Ren J, Sietsma D, Qiu S, Moessler H, Finklestein SP . Cerebrolysin enhances functional recovery following focal cerebral infarction in rats. Restor Neurol Neurosci. 2007;25:25–31.

[11]

10.1166/ajnn.2009.1010

[12]

Cerebrolysin enhances neurogenesis in the ischemic brain and improves functional outcome after stroke

Chunling Zhang, Michael Chopp, Yisheng Cui et al.

Journal of Neuroscience Research 10.1002/jnr.22495

[13]

10.1007/s00702-004-0248-2

[14]

Haffner Z, Gmeinbauer R, Moessler H . A randomized, double-blind, placebo-controlled trial with cerebrolysin in acute ischemic stroke [Abstract]. Cerebrovasc Dis. 2001;11:76.

[15]

Skvortsova VI, Stakhovskaia LV, Gubskii LV, Shamalov NA, Tikhonova IV, Smychkov AS . A randomized, doubleblind, placebo-controlled study of Cerebrolysin safety and efficacy in the treatment of acute ischemic stroke. Zh Nevrol Psikhiatr Im S S Korsakova. 2004;Suppl 11:51–55.

[16]

10.1111/j.1747-4949.2009.00340.x

[17]

ICH Topic E9 Statistical Principles for Clinical Trials Step 4 Consensus guideline February 5 1998 CPMP/ICH/363/96. Available at: http://www.ich.org/products/guidelines/efficacy/article/efficacy-guidelines.html. Accessed January 19 2012.

[18]

10.1161/01.str.27.11.2136

[19]

10.1080/01621459.1984.10478093

[20]

10.1002/sim.4780110903

[21]

10.1161/strokeaha.107.506378

[22]

10.1056/nejmoa0804656

[23]

10.1056/nejmoa052980

[24]

10.1001/jama.1995.03530130023023

[25]

10.1016/s0140-6736(98)08020-9

[26]

10.1056/nejmoa070240

[27]

10.1159/000091548

Cited By

102

Safety and Efficacy of Cerebrolysin for Neurorecovery After Acute Ischemic Stroke: A Systematic Review and Meta-Analysis of 14 Randomized Controlled Trials

Parag N Patel, Devang Mangal · 2025

Cureus

Endogenous defense mechanism-based neuroprotection in large-vessel acute ischemic stroke: A hope for future

Deepak Goel, Sushant Shangari · 2024

Brain Circulation

Neuroprotective agents in Acute Ischemic Stroke—A Reality Check

Luxitaa Goenka, Chakradhara Rao Uppugunduri Satyanarayana · 2019

Biomedicine & Pharmacotherapy

Metrics

102

Citations

27

References

Details

Published: Mar 01, 2012
Vol/Issue: 43(3)
Pages: 630-636

Authors

W

Wolf-Dieter Heiss

From the Max-Planck Institut für Neurologie (W.-D.H.), Koeln, Germany; the Department of Clinical Neurosciences (M.B.), Donau-Universität Krems, Krems, Austria; Tel-Aviv Sourasky Medical Center (N.M.B.), Tel Aviv, Israel; the Department of Public Health (J.T.), Hjelt Institute, University of Helsinki, Helsinki, Finland; and Hua Shan Hospital (Z.H.), Department of Neurology, Shanghai, PR China.

M

Michael Brainin

From the Max-Planck Institut für Neurologie (W.-D.H.), Koeln, Germany; the Department of Clinical Neurosciences (M.B.), Donau-Universität Krems, Krems, Austria; Tel-Aviv Sourasky Medical Center (N.M.B.), Tel Aviv, Israel; the Department of Public Health (J.T.), Hjelt Institute, University of Helsinki, Helsinki, Finland; and Hua Shan Hospital (Z.H.), Department of Neurology, Shanghai, PR China.

N

Natan M. Bornstein

From the Max-Planck Institut für Neurologie (W.-D.H.), Koeln, Germany; the Department of Clinical Neurosciences (M.B.), Donau-Universität Krems, Krems, Austria; Tel-Aviv Sourasky Medical Center (N.M.B.), Tel Aviv, Israel; the Department of Public Health (J.T.), Hjelt Institute, University of Helsinki, Helsinki, Finland; and Hua Shan Hospital (Z.H.), Department of Neurology, Shanghai, PR China.

J

Jaakko Tuomilehto

From the Max-Planck Institut für Neurologie (W.-D.H.), Koeln, Germany; the Department of Clinical Neurosciences (M.B.), Donau-Universität Krems, Krems, Austria; Tel-Aviv Sourasky Medical Center (N.M.B.), Tel Aviv, Israel; the Department of Public Health (J.T.), Hjelt Institute, University of Helsinki, Helsinki, Finland; and Hua Shan Hospital (Z.H.), Department of Neurology, Shanghai, PR China.

Z

Zhen Hong

From the Max-Planck Institut für Neurologie (W.-D.H.), Koeln, Germany; the Department of Clinical Neurosciences (M.B.), Donau-Universität Krems, Krems, Austria; Tel-Aviv Sourasky Medical Center (N.M.B.), Tel Aviv, Israel; the Department of Public Health (J.T.), Hjelt Institute, University of Helsinki, Helsinki, Finland; and Hua Shan Hospital (Z.H.), Department of Neurology, Shanghai, PR China.

Cite This Article

Wolf-Dieter Heiss, Michael Brainin, Natan M. Bornstein, et al. (2012). Cerebrolysin in Patients With Acute Ischemic Stroke in Asia. Stroke, 43(3), 630-636. https://doi.org/10.1161/strokeaha.111.628537

Cerebrolysin in Patients With Acute Ischemic Stroke in Asia

You May Also Like