An international study to investigate and optimise the safety of discontinuing valproate in young men and women with epilepsy: Protocol
Valproate is the most effective treatment for idiopathic generalised epilepsy. Currently, its use is restricted in women of childbearing potential owing to high teratogenicity. Recent evidence extended this risk to men's offspring, prompting recommendations to restrict use in everybody aged
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| Veröffentlicht in: | PloS one 2024-08, Vol.19 (8), p.e0306226 |
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| creator | Mbizvo, Gashirai K Martin, Glen P Sperrin, Matthew Bonnett, Laura J Schofield, Pieta Buchan, Iain Lip, Gregory Y H Marson, Anthony G |
| description | Valproate is the most effective treatment for idiopathic generalised epilepsy. Currently, its use is restricted in women of childbearing potential owing to high teratogenicity. Recent evidence extended this risk to men's offspring, prompting recommendations to restrict use in everybody aged |
| doi_str_mv | 10.1371/journal.pone.0306226 |
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Currently, its use is restricted in women of childbearing potential owing to high teratogenicity. Recent evidence extended this risk to men's offspring, prompting recommendations to restrict use in everybody aged <55 years. This study will evaluate mortality and morbidity risks associated with valproate withdrawal by emulating a hypothetical randomised-controlled trial (called a "target trial") using retrospective observational data. The data will be drawn from ~250m mainly US patients in the TriNetX repository and ~60m UK patients in Clinical Practice Research Datalink (CPRD). These will be scanned for individuals aged 16-54 years with epilepsy and on valproate who either continued, switched to lamotrigine or levetiracetam, or discontinued valproate between 2014-2024, creating four groups. Randomisation to these groups will be emulated by baseline confounder adjustment using g-methods. Mortality and morbidity outcomes will be assessed and compared between groups over 1-10 years, employing time-to-first-event and recurrent events analyses. A causal prediction model will be developed from these data to aid in predicting the safest alternative antiseizure medications. Together, these findings will optimise informed decision-making about valproate withdrawal and alternative treatment selection, providing immediate and vital information for patients, clinicians and regulators.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0306226</identifier><identifier>PMID: 39208329</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adolescent ; Adult ; Anticonvulsants - adverse effects ; Anticonvulsants - therapeutic use ; Care and treatment ; Codes ; Computer and Information Sciences ; Convulsions & seizures ; Decision making ; Demographic aspects ; Divalproex ; Dosage and administration ; Epilepsy ; Epilepsy - drug therapy ; Etiracetam ; Female ; Hospitals ; Humans ; Hypotheses ; International studies ; Lamotrigine ; Lamotrigine - adverse effects ; Lamotrigine - therapeutic use ; Levetiracetam - adverse effects ; Levetiracetam - therapeutic use ; Male ; Medicine and Health Sciences ; Middle Aged ; Morbidity ; Mortality ; Offspring ; Patient admissions ; Patient outcomes ; Patients ; Physical Sciences ; Prediction models ; Predictions ; Randomization ; Research and Analysis Methods ; Retrospective Studies ; Study Protocol ; Survival analysis ; Teratogenicity ; Valproic acid ; Valproic Acid - adverse effects ; Valproic Acid - therapeutic use ; Womens health ; Young Adult</subject><ispartof>PloS one, 2024-08, Vol.19 (8), p.e0306226</ispartof><rights>Copyright: © 2024 Mbizvo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</rights><rights>COPYRIGHT 2024 Public Library of Science</rights><rights>2024 Mbizvo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2024 Mbizvo et al 2024 Mbizvo et al</rights><rights>2024 Mbizvo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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Currently, its use is restricted in women of childbearing potential owing to high teratogenicity. Recent evidence extended this risk to men's offspring, prompting recommendations to restrict use in everybody aged <55 years. This study will evaluate mortality and morbidity risks associated with valproate withdrawal by emulating a hypothetical randomised-controlled trial (called a "target trial") using retrospective observational data. The data will be drawn from ~250m mainly US patients in the TriNetX repository and ~60m UK patients in Clinical Practice Research Datalink (CPRD). These will be scanned for individuals aged 16-54 years with epilepsy and on valproate who either continued, switched to lamotrigine or levetiracetam, or discontinued valproate between 2014-2024, creating four groups. Randomisation to these groups will be emulated by baseline confounder adjustment using g-methods. 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Currently, its use is restricted in women of childbearing potential owing to high teratogenicity. Recent evidence extended this risk to men's offspring, prompting recommendations to restrict use in everybody aged <55 years. This study will evaluate mortality and morbidity risks associated with valproate withdrawal by emulating a hypothetical randomised-controlled trial (called a "target trial") using retrospective observational data. The data will be drawn from ~250m mainly US patients in the TriNetX repository and ~60m UK patients in Clinical Practice Research Datalink (CPRD). These will be scanned for individuals aged 16-54 years with epilepsy and on valproate who either continued, switched to lamotrigine or levetiracetam, or discontinued valproate between 2014-2024, creating four groups. Randomisation to these groups will be emulated by baseline confounder adjustment using g-methods. 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| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2024-08, Vol.19 (8), p.e0306226 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_3098716098 |
| source | Public Library of Science (PLoS) Journals Open Access; MEDLINE; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adolescent Adult Anticonvulsants - adverse effects Anticonvulsants - therapeutic use Care and treatment Codes Computer and Information Sciences Convulsions & seizures Decision making Demographic aspects Divalproex Dosage and administration Epilepsy Epilepsy - drug therapy Etiracetam Female Hospitals Humans Hypotheses International studies Lamotrigine Lamotrigine - adverse effects Lamotrigine - therapeutic use Levetiracetam - adverse effects Levetiracetam - therapeutic use Male Medicine and Health Sciences Middle Aged Morbidity Mortality Offspring Patient admissions Patient outcomes Patients Physical Sciences Prediction models Predictions Randomization Research and Analysis Methods Retrospective Studies Study Protocol Survival analysis Teratogenicity Valproic acid Valproic Acid - adverse effects Valproic Acid - therapeutic use Womens health Young Adult |
| title | An international study to investigate and optimise the safety of discontinuing valproate in young men and women with epilepsy: Protocol |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-29T01%3A15%3A31IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=An%20international%20study%20to%20investigate%20and%20optimise%20the%20safety%20of%20discontinuing%20valproate%20in%20young%20men%20and%20women%20with%20epilepsy:%20Protocol&rft.jtitle=PloS%20one&rft.au=Mbizvo,%20Gashirai%20K&rft.date=2024-08-29&rft.volume=19&rft.issue=8&rft.spage=e0306226&rft.pages=e0306226-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0306226&rft_dat=%3Cgale_plos_%3EA806591364%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=3098716098&rft_id=info:pmid/39208329&rft_galeid=A806591364&rft_doaj_id=oai_doaj_org_article_add00988003b43b8b1d761bcbefad8e6&rfr_iscdi=true |