Biperiden Trial for Epilepsy Prevention

NCT04945213 | Recruiting Phase 3 DMC

• 2 other identifiers: AVAP-NG 198339005920810015461
• Study Type: interventional
• Target: 312
• Locations: 1 country
• Sites: 10

Brief Summary

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.

Conditions

Brain Injury Traumatic Moderate; Brain Injury Traumatic Severe; Post Traumatic Epilepsy

Keywords

Brain Injury; Epilepsy; Biperiden

Outcome Measures

Primary Outcomes (2)

• Incidence of Post Traumatic Epilepsy (PTE)

  Participants who present epileptic seizures will be compared between placebo and biperiden groups. Seizures will be counted starting 7 days after TBI and continuously during the following two years follow-up period. Patients and their relatives will be asked to keep a diary of seizures, and record all seizures with detailed descriptions of each event.

  7 days to 24 months

• Occurrence of Severe Adverse Events

  Proportion of participants that present at least one severe adverse event until 24 months after the traumatic brain injury will be compared between biperiden and placebo groups.

  24 months

Secondary Outcomes (12)

• Electroencephalogram Analyses: Presence of Epileptiform Discharges

  1,3, 6, 9,12,18 and 24 months

• Neuropsychological Assessments - semantic memory

  6 and 24 months

• Neuropsychological Assessments - visual construction

  6 and 24 months

• Neuropsychological Assessments - information processing speed and attention

  6 and 24 months

• Neuropsychological Assessments - short term memory

  6 and 24 months

Other Outcomes (2)

• Incidence of Mortality

  24 months

• Incidence of Non-Severe Adverse Events

  1,3, 6, 9,12,18 and 24 months

Study Arms (2)

Biperiden

EXPERIMENTAL

Drug: Biperiden 5mg of biperiden diluted in 100 ml of 0.9% saline - every 6 hours for 10 consecutive days - IV

Drug: Biperiden

Placebo

PLACEBO COMPARATOR

Placebo 1 mL of sterile vehicle (sodium lactate, lactic acid, sodium hydroxide and water for injections) diluted in 100 mL of 0,9% saline - every 6 hours for 10 consecutive days - IV

Other: Placebo

Interventions

Biperiden DRUG

5mg of biperiden diluted in 100 ml of 0.9% saline - every 6 hours for 10 consecutive days - IV

Also known as: Akineton

Biperiden

Placebo OTHER

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

Also known as: Sterile vehicle (sodium lactate, lactic acid, sodium hydroxide and water for injections)

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Given informed consent
• 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,

You may not qualify if:

• 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

Sponsors & Collaborators

• Hospital Sirio-Libanes: lead
• PROADI-SUS: collaborator
• Ministry of Health, Brazil: collaborator
• University of Sao Paulo: collaborator
• Santa Casa de Campo Grande: collaborator
• Hospital Sao Rafael: collaborator
• Santa Casa de Misericórdia de Sobral: collaborator
• Hospital de Clinicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo: collaborator
• Hospital São Paulo, Universidade Federal de São Paulo: collaborator
• Instituto Doutor José Frota: collaborator
• Hospital São Vicente de Paulo: collaborator

Study Sites (10)

Instituto Doutor José Frota

Fortaleza, Ceará, Brazil

NOT YET RECRUITING

Santa Casa de Misericórdia de Sobral

Sobral, Ceará, Brazil

RECRUITING

Hospital Estadual Urgencia e Emergencia -HEUE

Vitória, Espírito Santo, Brazil

NOT YET RECRUITING

Hospital São Rafael

Salvador, Estado de Bahia, Brazil

RECRUITING

Associação Beneficente Santa Casa de Campo Grande

Campo Grande, Mato Grosso do Sul, Brazil

RECRUITING

Hospital São Vicente de Paulo

Passo Fundo, Rio Grande do Sul, Brazil

ACTIVE NOT RECRUITING

Hospital das Clínicas da Faculdade de Medicina da Universidade de Ribeirão Preto

Ribeirão Preto, São Paulo, Brazil

RECRUITING

Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo

São Paulo, São Paulo, Brazil

RECRUITING

Hospital Sirio-Libanes

São Paulo, 01308-000, Brazil

RECRUITING

Hospital São Paulo, Universidade Federal de São Paulo

São Paulo, Brazil

NOT YET RECRUITING

Related Publications (15)

• Antoniuk SA. [Non-epileptic disorders in infancy and adolescence]. Medicina (B Aires). 2013;73 Suppl 1:71-6. Spanish.

  PMID: 24072054 BACKGROUND

• 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 BACKGROUND

• 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.

  BACKGROUND

• 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.

  BACKGROUND

• 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 BACKGROUND

• 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 29.

  PMID: 29096134 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• de Almeida CE, de Sousa Filho JL, Dourado JC, Gontijo PA, Dellaretti MA, Costa BS. Traumatic Brain Injury Epidemiology in Brazil. World Neurosurg. 2016 Mar;87:540-7. doi: 10.1016/j.wneu.2015.10.020. Epub 2015 Oct 17.

  PMID: 26485419 BACKGROUND

• DeVito NJ, Goldacre B. Catalogue of bias: publication bias. BMJ Evid Based Med. 2019 Apr;24(2):53-54. doi: 10.1136/bmjebm-2018-111107. Epub 2018 Dec 6. No abstract available.

  PMID: 30523135 BACKGROUND

• Englander J, Bushnik T, Duong TT, Cifu DX, Zafonte R, Wright J, Hughes R, Bergman W. Analyzing risk factors for late posttraumatic seizures: a prospective, multicenter investigation. Arch Phys Med Rehabil. 2003 Mar;84(3):365-73. doi: 10.1053/apmr.2003.50022.

  PMID: 12638104 BACKGROUND

• Husereau D, Drummond M, Petrou S, Carswell C, Moher D, Greenberg D, Augustovski F, Briggs AH, Mauskopf J, Loder E; CHEERS Task Force. Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement. Value Health. 2013 Mar-Apr;16(2):e1-5. doi: 10.1016/j.jval.2013.02.010.

  PMID: 23538200 BACKGROUND

• Benassi SK, Alves JGSM, Guidoreni CG, Massant CG, Queiroz CM, Garrido-Sanabria E, Loduca RDS, Susemihl MA, Paiva WS, de Andrade AF, Teixeira MJ, Andrade JQ, Garzon E, Foresti ML, Mello LE. Two decades of research towards a potential first anti-epileptic drug. Seizure. 2021 Aug;90:99-109. doi: 10.1016/j.seizure.2021.02.031. Epub 2021 Mar 3.

  PMID: 33714677 BACKGROUND

• Hauser WA, Annegers JF, Kurland LT. Prevalence of epilepsy in Rochester, Minnesota: 1940-1980. Epilepsia. 1991 Jul-Aug;32(4):429-45. doi: 10.1111/j.1528-1157.1991.tb04675.x.

  PMID: 1868801 BACKGROUND

• Foresti ML, Garzon E, Pinheiro CCG, Pacheco RL, Riera R, Mello LE. Biperiden for prevention of post-traumatic epilepsy: A protocol of a double-blinded placebo-controlled randomized clinical trial (BIPERIDEN trial). PLoS One. 2022 Sep 9;17(9):e0273584. doi: 10.1371/journal.pone.0273584. eCollection 2022.

  PMID: 36084082 DERIVED

MeSH Terms

Conditions

Epilepsy, Post-Traumatic; Brain Injuries; Epilepsy

Interventions

Biperiden; Sodium Lactate; Lactic Acid; Sodium Hydroxide; Water; Injections

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Bridged Bicyclo Compounds; Bridged-Ring Compounds; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azabicyclo Compounds; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring; Lactates; Hydroxy Acids; Carboxylic Acids; Hydroxides; Alkalies; Inorganic Chemicals; Anions; Ions; Electrolytes; Sodium Compounds; Oxides; Oxygen Compounds; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Luiz E Mello, MD, PhD

  Hospital Sirio-Libanês

  PRINCIPAL INVESTIGATOR

• Eliana Garzon, MD, PhD

  Hospital Sirio-Libanês

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Eliana Garzon, MD, PhD

CONTACT

+55 (11) 98206-2308; eliana.garzon@hsl.org.br

Maira L Foresti, PhD

CONTACT

+ 55(11) 958673803; mairalforesti@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 25, 2021
• First Posted: June 30, 2021
• Study Start: January 10, 2023
• Primary Completion (Estimated): December 20, 2026
• Study Completion (Estimated): December 20, 2026
• Last Updated: March 26, 2024

Record last verified: 2023-11

Locations

BR (10)