Antiepileptogenesis after stroke—trials and tribulations: Methodological challenges and recruitment results of a Phase II study with eslicarbazepine acetate
Abstract There is currently no evidence to support the use of antiseizure medications to prevent unprovoked seizures following stroke. Experimental animal models suggested a potential antiepileptogenic effect for eslicarbazepine acetate (ESL), and a Phase II, multicenter, randomized, double‐blind, p...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-09-01
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| Series: | Epilepsia Open |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/epi4.12735 |
| _version_ | 1797729147296940032 |
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| author | Matthias J. Koepp Eugen Trinka Yee‐Haur Mah Carla Bentes Susanne Knake Gian Luigi Gigli José M. Serratosa Johan Zelano Luís M. Magalhães Ana Pereira Joana Moreira Patrício Soares‐da‐Silva |
| author_facet | Matthias J. Koepp Eugen Trinka Yee‐Haur Mah Carla Bentes Susanne Knake Gian Luigi Gigli José M. Serratosa Johan Zelano Luís M. Magalhães Ana Pereira Joana Moreira Patrício Soares‐da‐Silva |
| author_sort | Matthias J. Koepp |
| collection | DOAJ |
| description | Abstract There is currently no evidence to support the use of antiseizure medications to prevent unprovoked seizures following stroke. Experimental animal models suggested a potential antiepileptogenic effect for eslicarbazepine acetate (ESL), and a Phase II, multicenter, randomized, double‐blind, placebo‐controlled study was designed to test this hypothesis and assess whether ESL treatment for 1 month can prevent unprovoked seizures following stroke. We outline the design and status of this antiepileptogenesis study, and discuss the challenges encountered in its execution to date. Patients at high risk of developing unprovoked seizures after acute intracerebral hemorrhage or acute ischemic stroke were randomized to receive ESL 800 mg/d or placebo, initiated within 120 hours after primary stroke occurrence. Treatment continued until Day 30, then tapered off. Patients could receive all necessary therapies for stroke treatment according to clinical practice guidelines and standard of care, and are being followed up for 18 months. The primary efficacy endpoint is the occurrence of a first unprovoked seizure within 6 months after randomization (“failure rate”). Secondary efficacy assessments include the occurrence of a first unprovoked seizure during 12 months after randomization and during the entire study; functional outcomes (Barthel Index original 10‐item version; National Institutes of Health Stroke Scale); post‐stroke depression (Patient Health Questionnaire‐9; PHQ‐9); and overall survival. Safety assessments include the evaluation of treatment‐emergent adverse events; laboratory parameters; vital signs; electrocardiogram; suicidal ideation and behavior (PHQ‐9 question 9). The protocol aimed to randomize approximately 200 patients (1:1), recruited from 21 sites in seven European countries and Israel. Despite the challenges encountered, particularly during the COVID‐19 pandemic, the study progressed and included a remarkable number of patients, with 129 screened and 125 randomized. Recruitment was stopped after 30 months, the first patient entered in May 2019, and the study is ongoing and following up on patients according to the Clinical Trial Protocol. |
| first_indexed | 2024-03-12T11:24:50Z |
| format | Article |
| id | doaj.art-1816a04c78354f59ba86372099a6f80a |
| institution | Directory Open Access Journal |
| issn | 2470-9239 |
| language | English |
| last_indexed | 2024-03-12T11:24:50Z |
| publishDate | 2023-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | Epilepsia Open |
| spelling | doaj.art-1816a04c78354f59ba86372099a6f80a2023-09-01T09:39:51ZengWileyEpilepsia Open2470-92392023-09-01831190120110.1002/epi4.12735Antiepileptogenesis after stroke—trials and tribulations: Methodological challenges and recruitment results of a Phase II study with eslicarbazepine acetateMatthias J. Koepp0Eugen Trinka1Yee‐Haur Mah2Carla Bentes3Susanne Knake4Gian Luigi Gigli5José M. Serratosa6Johan Zelano7Luís M. Magalhães8Ana Pereira9Joana Moreira10Patrício Soares‐da‐Silva11UCL Queen Square Institute of Neurology London UKDepartment of Neurology Christian‐Doppler University Hospital, Paracelsus Medical University, Centre for Cognitive Neuroscience, Member of EpiCARE Salzburg AustriaKing's College Hospital NHS Foundation Trust London UKReference Centre for Refractory Epilepsies (Member of EpiCARE) Hospital de Santa Maria‐CHULN Lisbon PortugalDepartment of Neurology, Epilepsy Centre Hessen Philipps‐University Marburg Marburg GermanyClinical Neurology Unit, Department of Medicine (DAME) University of Udine Udine ItalyDepartment of Neurology and Laboratory of Neurology, Fundación Instituto de Investigación Sanitaria‐Fundación Jiménez Díaz Autónoma University Madrid SpainInstitute of Neuroscience and Physiology, Sahlgrenska Academy University of Gothenburg Gothenburg SwedenBial—Portela & Cª, S.A. Coronado PortugalBial—Portela & Cª, S.A. Coronado PortugalBial—Portela & Cª, S.A. Coronado PortugalBial—Portela & Cª, S.A. Coronado PortugalAbstract There is currently no evidence to support the use of antiseizure medications to prevent unprovoked seizures following stroke. Experimental animal models suggested a potential antiepileptogenic effect for eslicarbazepine acetate (ESL), and a Phase II, multicenter, randomized, double‐blind, placebo‐controlled study was designed to test this hypothesis and assess whether ESL treatment for 1 month can prevent unprovoked seizures following stroke. We outline the design and status of this antiepileptogenesis study, and discuss the challenges encountered in its execution to date. Patients at high risk of developing unprovoked seizures after acute intracerebral hemorrhage or acute ischemic stroke were randomized to receive ESL 800 mg/d or placebo, initiated within 120 hours after primary stroke occurrence. Treatment continued until Day 30, then tapered off. Patients could receive all necessary therapies for stroke treatment according to clinical practice guidelines and standard of care, and are being followed up for 18 months. The primary efficacy endpoint is the occurrence of a first unprovoked seizure within 6 months after randomization (“failure rate”). Secondary efficacy assessments include the occurrence of a first unprovoked seizure during 12 months after randomization and during the entire study; functional outcomes (Barthel Index original 10‐item version; National Institutes of Health Stroke Scale); post‐stroke depression (Patient Health Questionnaire‐9; PHQ‐9); and overall survival. Safety assessments include the evaluation of treatment‐emergent adverse events; laboratory parameters; vital signs; electrocardiogram; suicidal ideation and behavior (PHQ‐9 question 9). The protocol aimed to randomize approximately 200 patients (1:1), recruited from 21 sites in seven European countries and Israel. Despite the challenges encountered, particularly during the COVID‐19 pandemic, the study progressed and included a remarkable number of patients, with 129 screened and 125 randomized. Recruitment was stopped after 30 months, the first patient entered in May 2019, and the study is ongoing and following up on patients according to the Clinical Trial Protocol.https://doi.org/10.1002/epi4.12735acute intracerebral hemorrhage or infarctantiseizure medicationepilepsyepileptogenesisunprovoked seizure |
| spellingShingle | Matthias J. Koepp Eugen Trinka Yee‐Haur Mah Carla Bentes Susanne Knake Gian Luigi Gigli José M. Serratosa Johan Zelano Luís M. Magalhães Ana Pereira Joana Moreira Patrício Soares‐da‐Silva Antiepileptogenesis after stroke—trials and tribulations: Methodological challenges and recruitment results of a Phase II study with eslicarbazepine acetate Epilepsia Open acute intracerebral hemorrhage or infarct antiseizure medication epilepsy epileptogenesis unprovoked seizure |
| title | Antiepileptogenesis after stroke—trials and tribulations: Methodological challenges and recruitment results of a Phase II study with eslicarbazepine acetate |
| title_full | Antiepileptogenesis after stroke—trials and tribulations: Methodological challenges and recruitment results of a Phase II study with eslicarbazepine acetate |
| title_fullStr | Antiepileptogenesis after stroke—trials and tribulations: Methodological challenges and recruitment results of a Phase II study with eslicarbazepine acetate |
| title_full_unstemmed | Antiepileptogenesis after stroke—trials and tribulations: Methodological challenges and recruitment results of a Phase II study with eslicarbazepine acetate |
| title_short | Antiepileptogenesis after stroke—trials and tribulations: Methodological challenges and recruitment results of a Phase II study with eslicarbazepine acetate |
| title_sort | antiepileptogenesis after stroke trials and tribulations methodological challenges and recruitment results of a phase ii study with eslicarbazepine acetate |
| topic | acute intracerebral hemorrhage or infarct antiseizure medication epilepsy epileptogenesis unprovoked seizure |
| url | https://doi.org/10.1002/epi4.12735 |
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