nnpNeurology, Neuropsychiatry, PsychosomaticsНеврология, нейропсихиатрия, психосоматика2074-27112310-1342"IMA-Press", LLC10.14412/2074-2711-2012-426nnp-166Research ArticleArticlesСтатьиCiticoline for ischemic stroke: ICTUS trialЦитиколин при ишемическом инсульте: исследование ICTUSParfenovVladimir AnatolyevichParfenovVladimir Anatolyevich

Clinic and Department of Nervous System Diseases

Clinic and Department of Nervous System Diseases

vladimirparfenov@mail.ru20121512201244NO4 (2012)7176Copyright © Parfenov V.A., 20122012Parfenov V.A.Parfenov V.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://nnp.ima-press.net/nnp/article/view/166

The paper gives data available in the literature on the use of citicoline in an experimental model of ischemic stroke (IS) and in randomized multicenter placebo-controlled trials. It analyzes the results of the ICTUS trial in which 2298 patients with IS who received randomly citicoline or placebo for 24 hours after the onset of symptoms (I000 mg intravenously every I2 hours during the first 3 days, then orally as one 500-mg tablet every 12 hours during 6 weeks). The results of the trial confirmed the safety of citicoline used in IS, but failed to show its significant advantage over placebo in reducing the degree of disability (global improvement) 90 days later. However, to pool the results of the ICTUS trial with those of other randomized multicenter placebo-controlled studies demonstrates a significant decrease in the degree of disability in IS patients treated with citicoline.

Представлены данные литературы об использовании цитиколина в экспериментальной модели ишемического инсульта (ИИ) и рандомизированных многоцентровых плацебоконтролируемых исследованиях. Анализируются результаты исследования ICTUS, в котором 2298 пациентов с ИИ методом рандомизации получали цитиколин или плацебо в течение 24 ч после появления симптомов (I000 мг каждые I2 ч внутривенно в течение первых 3 дней, затем перорально по I таблетке 500 мг каждые I2 ч) на протяжении 6 нед. Результаты исследования подтвердили безопасность применения цитиколина при ИИ, но не показали его достоверного преимущества перед плацебо в отношении уменьшения степени инвалидизации (глобальное улучшение) через 90 дней. Однако объединение результатов ICTUS с данными других рандомизированных многоцентровых плацебоконтролируемых исследований показывает достоверное уменьшение степени инвалидности у больных ИИ при использовании цитиколина.

ишемический инсультцитиколинисследование ICTUSischemic strokeciticolineICTUS trialReferences<div><p>Дамулин И.В., Парфенов В.А., Скоромец А.А. и др. Нарушения кровообращения в головном и спинном мозге. В кн.: Болезни нервной системы. Рук-во для врачей. Под ред. Н.Н. Яхно. Т.1. М.: Медицина, 2005; 232-303.</p><p>Инсульт: диагностика, лечение и профилактика. Под ред. З.А. Суслиной, М.А. Пирадова. М.: МЕДпресс-информ, 2008;288 с.</p><p>European Stroke Organisation (ESO) Executive Committee; ESO Writing Committee. Guidelines for management of ischaemic stroke and transient ischaemic attack. Cerebrovasc Dis 2008;25:457-507.</p><p>Скворцова В.И., Губский Л.В., Стаховская Л.В. и др. Ишемический инсульт. В кн.: Неврология, национальное руководство. Под ред. Е.И. Гусева, А.И. Коновалова, В.И. Скворцовой. М.: ГЭОТАР-Медиа, 2009;592-615.</p><p>Adams H.P., del Zoppo G.Jr, Alberts M.J. Guidelines for the Early Management of Adults With Ischemic Stroke: A Guideline From the American Heart Association. American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: The American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists. Stroke 2007;38:1655—711.</p><p>Парфенов В.А., Хасанова Д.Р. Ишемический инсульт. М.: МИА, 2012;288 с.</p><p>Lozano Fernandez R. Efficacy and safety of oral CDP-choline. Drug surveillance study in 2817 cases. Arzneimittelforsch 1983;33:1073-80.</p><p>Conant R., Schauss A.G. Therapeutic Applications of Citicoline for Stroke and Cognitive Dysfunction in the Elderly: A Review of the Literature. Altern Med Rev 2004;9:17-31.</p><p>Schabitz W.R., Weber J., Takano K. et al. The effects of prolonged treatment with citicoline in temporary experimental focal ischemia. J Neurol Sci 1996;138:21-5.</p><p>Hurtado O., Cardenas A., Pradillo J.M. et al. A chronic treatment with CDP-choline improves functional recovery and increases neuronal plasticity after experimental stroke. Neurobiol Dis 2007;26:105-11.</p><p>Andersen M., Overgaard K., Meden P. et al. Effects of citicoline combined with thrombolytic therapy in a rat embolic stroke model. Stroke 1999;30:1464-71.</p><p>Gutierrez-Fernandez M., Lecinana M.A., Rodriguez-Frutos B. et al. CDP-choline at high doses is as effective as i.v. thrombolysis in experimental animal stroke. Neurol Res 2012;34:649-56.</p><p>Bustamante A., Giralt D., Garcia-Bonilla L. et al. Citicoline in pre-clinical animal models of stroke: a meta-analysis shows the optimal neuroprotective profile and the missing steps for jumping into a stroke clinical trial. J Neurochem 2012;123:217-25.</p><p>Tazaki Y., Sakai F., Otomo E. et al. Treatment of acute cerebral infarction with a choline precursor in a multicenter double-blind placebo-controlled study. Stroke 1988;19:211-6.</p><p>Clark W.M., Warach S.J., Pettigrew L.C. et al. A randomized dose-response trial of citicoline in acute ischemic stroke patients. Citicoline Stroke Study Group. Neurology 1997;49:671-8.</p><p>Clark W.M., Williams B.J., Selzer K.A. et al. A randomized efficacy trial of citicoline in patients with acute ischemic stroke. Stroke 1999;30:2592-7.</p><p>Clark W.M., Wechsler L.R., Sabounjian L.A. et al. Citicoline Stroke Study Group. A phase III randomized efficacy trial of 2000 mg citicoline in acute ischemic stroke patients. Neurology 2001;57:1595-602.</p><p>Davalos A., Castillo J., Alvarez-Sabin J. et al. Oral citicoline in acute ischemic stroke: an individual patient data pooling analysis of clinical trials. Stroke 2002;33:2850-7.</p><p>Davalos A., Alvarez-Sabin J., Castillo J. et al. Citicoline in the treatment of acute ischaemic stroke: an international, randomised, multicentre, placebo-controlled study (ICTUS trial). Lancet 2012;380:349-57.</p><p>Hankey G.J. How effective is citicoline for acute ischaemic stroke? Lancet 2012;380:318-20.</p></div><br /><div><p>Дамулин И.В., Парфенов В.А., Скоромец А.А. и др. Нарушения кровообращения в головном и спинном мозге. В кн.: Болезни нервной системы. Рук-во для врачей. Под ред. Н.Н. Яхно. Т.1. М.: Медицина, 2005; 232-303.</p><p>Инсульт: диагностика, лечение и профилактика. Под ред. З.А. Суслиной, М.А. Пирадова. М.: МЕДпресс-информ, 2008;288 с.</p><p>European Stroke Organisation (ESO) Executive Committee; ESO Writing Committee. Guidelines for management of ischaemic stroke and transient ischaemic attack. Cerebrovasc Dis 2008;25:457-507.</p><p>Скворцова В.И., Губский Л.В., Стаховская Л.В. и др. Ишемический инсульт. В кн.: Неврология, национальное руководство. Под ред. Е.И. Гусева, А.И. Коновалова, В.И. Скворцовой. М.: ГЭОТАР-Медиа, 2009;592-615.</p><p>Adams H.P., del Zoppo G.Jr, Alberts M.J. Guidelines for the Early Management of Adults With Ischemic Stroke: A Guideline From the American Heart Association. American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: The American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists. Stroke 2007;38:1655—711.</p><p>Парфенов В.А., Хасанова Д.Р. Ишемический инсульт. М.: МИА, 2012;288 с.</p><p>Lozano Fernandez R. Efficacy and safety of oral CDP-choline. Drug surveillance study in 2817 cases. Arzneimittelforsch 1983;33:1073-80.</p><p>Conant R., Schauss A.G. Therapeutic Applications of Citicoline for Stroke and Cognitive Dysfunction in the Elderly: A Review of the Literature. Altern Med Rev 2004;9:17-31.</p><p>Schabitz W.R., Weber J., Takano K. et al. The effects of prolonged treatment with citicoline in temporary experimental focal ischemia. J Neurol Sci 1996;138:21-5.</p><p>Hurtado O., Cardenas A., Pradillo J.M. et al. A chronic treatment with CDP-choline improves functional recovery and increases neuronal plasticity after experimental stroke. Neurobiol Dis 2007;26:105-11.</p><p>Andersen M., Overgaard K., Meden P. et al. Effects of citicoline combined with thrombolytic therapy in a rat embolic stroke model. Stroke 1999;30:1464-71.</p><p>Gutierrez-Fernandez M., Lecinana M.A., Rodriguez-Frutos B. et al. CDP-choline at high doses is as effective as i.v. thrombolysis in experimental animal stroke. Neurol Res 2012;34:649-56.</p><p>Bustamante A., Giralt D., Garcia-Bonilla L. et al. Citicoline in pre-clinical animal models of stroke: a meta-analysis shows the optimal neuroprotective profile and the missing steps for jumping into a stroke clinical trial. J Neurochem 2012;123:217-25.</p><p>Tazaki Y., Sakai F., Otomo E. et al. Treatment of acute cerebral infarction with a choline precursor in a multicenter double-blind placebo-controlled study. Stroke 1988;19:211-6.</p><p>Clark W.M., Warach S.J., Pettigrew L.C. et al. A randomized dose-response trial of citicoline in acute ischemic stroke patients. Citicoline Stroke Study Group. Neurology 1997;49:671-8.</p><p>Clark W.M., Williams B.J., Selzer K.A. et al. A randomized efficacy trial of citicoline in patients with acute ischemic stroke. Stroke 1999;30:2592-7.</p><p>Clark W.M., Wechsler L.R., Sabounjian L.A. et al. Citicoline Stroke Study Group. A phase III randomized efficacy trial of 2000 mg citicoline in acute ischemic stroke patients. Neurology 2001;57:1595-602.</p><p>Davalos A., Castillo J., Alvarez-Sabin J. et al. Oral citicoline in acute ischemic stroke: an individual patient data pooling analysis of clinical trials. Stroke 2002;33:2850-7.</p><p>Davalos A., Alvarez-Sabin J., Castillo J. et al. Citicoline in the treatment of acute ischaemic stroke: an international, randomised, multicentre, placebo-controlled study (ICTUS trial). Lancet 2012;380:349-57.</p><p>Hankey G.J. How effective is citicoline for acute ischaemic stroke? Lancet 2012;380:318-20.</p></div><br />

The authors declare that there are no conflicts of interest present.