{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T20:24:14Z","timestamp":1790108654652,"version":"4.0.1"},"reference-count":25,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2022,9,9]],"date-time":"2022-09-09T00:00:00Z","timestamp":1662681600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Programa de Apoio ao Desenvolvimento Institucional do Sistema \u00danico de Sa\u00fade","award":["25000.014325\/2021-33"],"award-info":[{"award-number":["25000.014325\/2021-33"]}]},{"name":"Funda\u00e7\u00e3o de Amparo a Pesquisa do Estado de S\u00e3o Paulo","award":["18\/24561-5"],"award-info":[{"award-number":["18\/24561-5"]}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["311619\/2019-3"],"award-info":[{"award-number":["311619\/2019-3"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Traumatic brain injury (TBI) is one of the most important causes of acquired structural epilepsy, post-traumatic epilepsy (PTE), however, efficient preventative measures and treatment are still not available to patients. Preclinical studies indicated biperiden, an anticholinergic drug, as a potential drug to modify the epileptogenic process. The main objective of this clinical trial is to evaluate the efficacy of biperiden as an antiepileptogenic agent in patients that suffered TBI.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>This prospective multicenter (n = 10) interventional study will include 312 adult patients admitted to emergency care units with a diagnosis of moderate or severe TBI. Following inclusion and exclusion criteria, patients will be randomized, using block randomization, to receive double-blind treatment with placebo or biperiden for 10 days. Follow-up will occur at specific time windows up to 2 years. Main outcomes are incidence of PTE after TBI and occurrence of severe adverse events. Other outcomes include exploratory investigation of factors that might have benefits for the treatment or might influence its results, such as genetic background, clinical progression, electroencephalographic abnormalities, health-related quality of life and neuropsychological status. Analyses will be conducted following the safety, intention-to-treat and efficacy concepts.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Discussion<\/jats:title>\n<jats:p>We hypothesize that biperiden treatment will be effective to prevent or mitigate the development of post-traumatic epilepsy in TBI patients. Other health measures from this population also may benefit from treatment with biperiden.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Trial registration<\/jats:title>\n<jats:p>ClinicalTrials.gov, <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04945213\" xlink:type=\"simple\">NCT04945213<\/jats:ext-link>. Registered on June 30, 2021.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0273584","type":"journal-article","created":{"date-parts":[[2022,9,9]],"date-time":"2022-09-09T20:49:28Z","timestamp":1662756568000},"page":"e0273584","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":10,"title":["Biperiden for prevention of post-traumatic epilepsy: A protocol of a double-blinded placebo-controlled randomized clinical trial (BIPERIDEN trial)"],"prefix":"10.1371","volume":"17","author":[{"given":"Maira Licia","family":"Foresti","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliana","family":"Garzon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7613-6997","authenticated-orcid":true,"given":"Carla Cristina 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