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Идёт набор NCT04945213

Biperiden Trial for Epilepsy Prevention

Фаза III С лечением Brain Injury Traumatic Moderate Brain Injury Traumatic Severe Post Traumatic Epilepsy

Ориентир для пациента и семьи

Простыми словами

Автоматическая сводка по структурированным данным реестра. Она помогает сориентироваться, но не заменяет официальный протокол или оценку врача.

Что изучают
В протоколе указаны: Biperiden, Placebo.
Кому может быть актуально
Состояния в реестре: Brain Injury Traumatic Moderate, Brain Injury Traumatic Severe, Post Traumatic Epilepsy. Базовые параметры: 18 лет — 75 лет · Все.
Что важно проверить
Возраст, диагноз и пол — только базовые ориентиры. Предыдущее лечение, анализы и другие обязательные условия указаны ниже в критериях участия.
Где проводится
Бразилия
Следующий шаг
Сохраните исследование, покажите его лечащему врачу и уточните актуальный статус у исследовательского центра. Расходы, документы и поездка →

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Официальное название

Biperiden for Prevention of Epilepsy in Patients With Traumatic Brain Injury

Обзор

One of the most important neurological consequences following Traumatic Brain Injury (TBI) is the development of post traumatic epilepsy (PTE). Nevertheless, there is still no effective therapeutic intervention to reduce the occurrence of PTE. In previous studies with animals models of epilepsy, the biperiden decreased the incidence and intensity of spontaneous epileptic seizures besides delaying their appearance. The aim of this study is the evaluation of biperiden as antiepileptogenic drug to prevent PTE and also the determination of side effects, evaluating its cost-effectiveness in patients with moderate and severe TBI.

Подробное описание

One of the most important neurological consequences following Traumatic Brain Injury (TBI) is the development of post traumatic epilepsy (PTE), which accounts for 5% of all epilepsy etiologies in the general population. This makes TBI one of the most important causes of secondary epilepsy, overcoming other causes such as infections, drug abuse or familiar history of epilepsy. The occurrence of spontaneous epileptic seizures after TBI, mostly starting in the first 2 years after moderate or severe TBI, might be as high as 86%, specially in those with a single acute symptomatic seizure, with remission rates of 25-40%. The causative relationship between TBI and epilepsy, as well as other types of epilepsy in general, are still not completely understood and PTE is not yet preventable.

The therapeutic approach indicated for TBI may involve medications, surgical procedures or both, with no effective therapeutic intervention to reduce its occurrence. Several experimental studies in animal models have shown that drugs, which modify processes of neuronal plasticity, have the potential to modify the natural course of PTE. Among these, biperiden (anti-cholinergic indicated for Parkinson's disease) has shown reduction in the incidence and intensity of spontaneous epileptic seizures and also delayed their occurence in animal epilepsy model. Thus Biperiden would be an excellent candidate for an antiepileptogenic agent. It is intended here to test its effectiveness and safety in adult patients, victims of moderate and severe TBI. Patients will be randomized to receive 5 mg of Biperiden iv, diluted in 100 ml of 0.9% saline (treatment group) or 1 mL of sterile vehicle (sodium lactate, lactic acid, sodium hydroxide and water for injections) diluted in 100 mL of 0,9% saline (placebo group), every 6 hours for 10 days after TBI. Prospectively, patients will be followed up for two years, on periodic visits to assess the development of epileptic seizures. Other factors that might have benefits with the treatment, such as epileptiform abnormalities, genetic markers and neuropsychological aspects, will also be evaluated. The results could be important for a better comprehension of basic mechanisms of epilepsy development. Side effects of Biperiden use, at high doses during a short period of time, will be measured. If Biperiden is efficient and safe, it will certainly be a low-cost option for Brazilian public health system (SUS).

Вмешательства

  • Препарат Biperiden
    5mg of biperiden diluted in 100 ml of 0.9% saline - every 6 hours for 10 consecutive days - IV
  • Другое Placebo
    1ml sterile vehicle (sodium lactate, lactic acid, sodium hydroxide and water for injections) diluted in 100 ml 0.9% saline - every 6 hours for 10 consecutive days - IV

Первичные конечные точки

  • Incidence of Post Traumatic Epilepsy (PTE) [Срок оценки: 7 days to 24 months]
  • Occurrence of Severe Adverse Events [Срок оценки: 24 months]
Вторичные конечные точки (12)
  • Electroencephalogram Analyses: Presence of Epileptiform Discharges [Срок оценки: 1,3, 6, 9,12,18 and 24 months]
  • Neuropsychological Assessments - semantic memory [Срок оценки: 6 and 24 months]
  • Neuropsychological Assessments - visual construction [Срок оценки: 6 and 24 months]
  • Neuropsychological Assessments - information processing speed and attention [Срок оценки: 6 and 24 months]
  • Neuropsychological Assessments - short term memory [Срок оценки: 6 and 24 months]
  • Neuropsychological Assessments - visual construction and visuospatial long-term memory [Срок оценки: 6 and 24 months]
  • Neuropsychological Assessments - verbal long-term memory [Срок оценки: 6 and 24 months]
  • Neuropsychological Assessments - executive functions [Срок оценки: 6 and 24 months]
  • Health-related quality of life assessment - EQ-5D-3L descriptive system [Срок оценки: 3, 6, 12 and 24 months]
  • Health-related quality of life assessment - EQ-VAS self-rated health [Срок оценки: 3, 6, 12 and 24 months]
  • Biomarkers - Expression of the ApoEϵ4 allele [ Time Frame: 10 days after TBI ] [Срок оценки: Up to 10 days after TBI]
  • Incidence of Post Traumatic Epilepsy (PTE) during the Follow-up [Срок оценки: 1,3, 6, 9,12,18 and 24 months]

Критерии участия

Критерии включения

  • Given informed consent
  • 18 - 75 years of age
  • GCS between 6 and 12 at hospital admission. GCS between 3 and 5 at hospital admission can be enrolled if patient was sedated at the accident scene with previous GCS between 6 and 15.
  • Moderate or severe acute traumatic brain injury
  • All genders
  • Brain CT scan with signs of of acute intraparenchymal hemorrhage and/or contusion
  • Able to receive the first dose of treatment or placebo within 18 hours of brain injury,

Критерии исключения

  • Previous use of biperiden
  • History of epilepsy (confirmed by patient chart)
  • History of seizures or use of antiepileptic medication
  • Pregnancy
  • Participation in another clinical trial at the time of randomization
  • History of neoplasia, neurodegenerative diseases; history of stroke, cognitive impairment, benign prostatic hyperplasia, atrioventricular block or any other cardiac arrhythmia, or glaucoma megacolon or mechanical obstruction
  • Homeless patient

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение
Рандомизированное
Модель
Параллельные группы
Маскирование
Четверное слепое
Основная цель
Профилактика

Центры проведения

Бразилия · 10 центров
  • Instituto Doutor José Frota — Fortaleza
  • Santa Casa de Misericórdia de Sobral — Sobral
  • Hospital Estadual Urgencia e Emergencia -HEUE — Vitória
  • Hospital São Rafael — Salvador
  • Associação Beneficente Santa Casa de Campo Grande — Campo Grande
  • Hospital São Vicente de Paulo — Passo Fundo
  • Hospital das Clínicas da Faculdade de Medicina da Universidade de Ribeirão Preto — Ribeirão Preto
  • Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo — São Paulo
  • … и ещё 2 центра

Публикации

  • Antoniuk SA. [Non-epileptic disorders in infancy and adolescence]. Medicina (B Aires). 2013;73 Suppl 1:71-6. Spanish. PMID 24072054
  • Annegers JF, Hauser WA, Coan SP, Rocca WA. A population-based study of seizures after traumatic brain injuries. N Engl J Med. 1998 Jan 1;338(1):20-4. doi: 10.1056/NEJM199801013380104. PMID 9414327
  • Aronstam, RS & Patil, P. Muscarinic Receptors: Autonomic Neurons, Encyclopedia of Neuroscience, Academic Press,2009; 1141-1149, ISBN 9780080450469, https://doi.org/10.1016/B978-008045046-9.00692-6.
  • Anvisa. MANUAL PARA NOTIFICAÇÃO DE EVENTOS ADVERSOS E MONITORAMENTO DE SEGURANÇA EM ENSAIOS CLÍNICOS - 1a. edição. 2016. Disponível em: http://portal.anvisa.gov.br/documents/33836/2492465/Manual+para+Notifica%C3%A7%C3%A3o+de+Eventos+Adversos+e+Monitoramento+de+Seguran%C3%A7a+em+Ensaios+Cl%C3%ADnicos+-+1%C2%AA+Edi%C3%A7%C3%A3o/04a68574-8aac-43c9-b0b2-7b7cd80831c4. Acessado em 5 de novembro de 2019.
  • Brady RD, Casillas-Espinosa PM, Agoston DV, Bertram EH, Kamnaksh A, Semple BD, Shultz SR. Modelling traumatic brain injury and posttraumatic epilepsy in rodents. Neurobiol Dis. 2019 Mar;123:8-19. doi: 10.1016/j.nbd.2018.08.007. Epub 2018 Aug 16. PMID 30121231
  • Bittencourt S, Ferrazoli E, Valente MF, Romariz S, Janisset NRLL, Macedo CE, Antonio BB, Barros V, Mundim M, Porcionatto M, Aarao MC, Miranda MF, Rodrigues AM, de Almeida AG, Longo BM, Mello LE. Modification of the natural progression of epileptogenesis by means of biperiden in the pilocarpine model of epilepsy. Epilepsy Res. 2017 Dec;138:88-97. doi: 10.1016/j.eplepsyres.2017.10.019. Epub 2017 Oct PMID 29096134
  • D'Ambrosio R, Perucca E. Epilepsy after head injury. Curr Opin Neurol. 2004 Dec;17(6):731-5. doi: 10.1097/00019052-200412000-00014. PMID 15542983
  • da Silva AM, Vaz AR, Ribeiro I, Melo AR, Nune B, Correia M. Controversies in posttraumatic epilepsy. Acta Neurochir Suppl (Wien). 1990;50:48-51. doi: 10.1007/978-3-7091-9104-0_9. PMID 2129092

Идентификаторы

NCT: NCT04945213 · AVAP-NG 1983 · 39005920810015461

Первоисточники (государственные реестры)

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