Pavel Klein, Daniel Herr, Phillip L Pearl, JoAnne Natale, Zachary Levine, Claude Nogay, Fabian Sandoval, Stacey Trzcinski, Shireen M Atabaki, Tammy Tsuchida, John van den Anker, Steven J Soldin, Jianping He, Robert McCarter
{"title":"左乙拉西坦预防创伤后癫痫的2期安全性和可行性研究结果。","authors":"Pavel Klein, Daniel Herr, Phillip L Pearl, JoAnne Natale, Zachary Levine, Claude Nogay, Fabian Sandoval, Stacey Trzcinski, Shireen M Atabaki, Tammy Tsuchida, John van den Anker, Steven J Soldin, Jianping He, Robert McCarter","doi":"10.1001/archneurol.2012.445","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>To evaluate the safety and tolerability of treatment with levetiracetam and determine the trough levels of levetiracetam in patients with traumatic brain injury (TBI) who are at high risk for posttraumatic epilepsy (PTE).</p><p><strong>Design: </strong>Open-label, nonrandomized phase 2 study with 2 arms comparing levetiracetam treatment vs observation.</p><p><strong>Setting: </strong>Two level 1 trauma centers.</p><p><strong>Patients: </strong>A total of 422 participants 6 years or older with TBI who have a 20% risk for PTE were screened. Of these participants, 205 (48.6%) were eligible. A total of 126 participants were enrolled: 86 adults and 40 children. A total of 66 participants were in the treatment group (46 adults and 20 children), and a total of 60 participants were in the observation group (40 adults and 20 children). Participants presenting within 8 hours after TBI received treatment, and those presenting more than 8 to 24 hours after TBI did not.</p><p><strong>Intervention: </strong>Treatment with levetiracetam (55 mg/kg/d) for 30 days starting within 8 hours after injury.</p><p><strong>Main outcome measures: </strong>Number of adverse events, mood score, number of infections, trough level of levetiracetam, and PTE.</p><p><strong>Results: </strong>Of the 66 participants treated with levetiracetam, 2 (3%) stopped treatment owing to toxicity (somnolence). The most common adverse events were fatigue, headache, and somnolence. Mood scores and number of infections did not differ between the treatment and observation groups. Mean trough levels of levetiracetam on days 2 to 30 ranged from 19.6 to 26.7 μg/mL. At 2 years, 13 of 86 adults (15.1%) and 1 of 40 children (2.5%) developed PTE. At 2 years, 5 of 46 treated adults (10.9%) and 8 of 40 untreated adults (20.0%) developed PTE (relative risk, 0.47; P=.18).</p><p><strong>Conclusion: </strong>Treatment with 55 mg/kg/d of levetiracetam (a dose with an antiepileptogenic effect on animals) for patients with TBI at risk for PTE is safe and well tolerated, with plasma levels similar to those in animal studies. The findings support further evaluation of levetiracetam treatment for the prevention of PTE.</p><p><strong>Trial registration: </strong>clinicaltrials.gov Identifier: NCT01463033.</p>","PeriodicalId":8321,"journal":{"name":"Archives of neurology","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2012-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1001/archneurol.2012.445","citationCount":"76","resultStr":"{\"title\":\"Results of phase 2 safety and feasibility study of treatment with levetiracetam for prevention of posttraumatic epilepsy.\",\"authors\":\"Pavel Klein, Daniel Herr, Phillip L Pearl, JoAnne Natale, Zachary Levine, Claude Nogay, Fabian Sandoval, Stacey Trzcinski, Shireen M Atabaki, Tammy Tsuchida, John van den Anker, Steven J Soldin, Jianping He, Robert McCarter\",\"doi\":\"10.1001/archneurol.2012.445\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objectives: </strong>To evaluate the safety and tolerability of treatment with levetiracetam and determine the trough levels of levetiracetam in patients with traumatic brain injury (TBI) who are at high risk for posttraumatic epilepsy (PTE).</p><p><strong>Design: </strong>Open-label, nonrandomized phase 2 study with 2 arms comparing levetiracetam treatment vs observation.</p><p><strong>Setting: </strong>Two level 1 trauma centers.</p><p><strong>Patients: </strong>A total of 422 participants 6 years or older with TBI who have a 20% risk for PTE were screened. Of these participants, 205 (48.6%) were eligible. A total of 126 participants were enrolled: 86 adults and 40 children. A total of 66 participants were in the treatment group (46 adults and 20 children), and a total of 60 participants were in the observation group (40 adults and 20 children). Participants presenting within 8 hours after TBI received treatment, and those presenting more than 8 to 24 hours after TBI did not.</p><p><strong>Intervention: </strong>Treatment with levetiracetam (55 mg/kg/d) for 30 days starting within 8 hours after injury.</p><p><strong>Main outcome measures: </strong>Number of adverse events, mood score, number of infections, trough level of levetiracetam, and PTE.</p><p><strong>Results: </strong>Of the 66 participants treated with levetiracetam, 2 (3%) stopped treatment owing to toxicity (somnolence). The most common adverse events were fatigue, headache, and somnolence. Mood scores and number of infections did not differ between the treatment and observation groups. Mean trough levels of levetiracetam on days 2 to 30 ranged from 19.6 to 26.7 μg/mL. At 2 years, 13 of 86 adults (15.1%) and 1 of 40 children (2.5%) developed PTE. At 2 years, 5 of 46 treated adults (10.9%) and 8 of 40 untreated adults (20.0%) developed PTE (relative risk, 0.47; P=.18).</p><p><strong>Conclusion: </strong>Treatment with 55 mg/kg/d of levetiracetam (a dose with an antiepileptogenic effect on animals) for patients with TBI at risk for PTE is safe and well tolerated, with plasma levels similar to those in animal studies. The findings support further evaluation of levetiracetam treatment for the prevention of PTE.</p><p><strong>Trial registration: </strong>clinicaltrials.gov Identifier: NCT01463033.</p>\",\"PeriodicalId\":8321,\"journal\":{\"name\":\"Archives of neurology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2012-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1001/archneurol.2012.445\",\"citationCount\":\"76\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Archives of neurology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1001/archneurol.2012.445\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Archives of neurology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1001/archneurol.2012.445","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Results of phase 2 safety and feasibility study of treatment with levetiracetam for prevention of posttraumatic epilepsy.
Objectives: To evaluate the safety and tolerability of treatment with levetiracetam and determine the trough levels of levetiracetam in patients with traumatic brain injury (TBI) who are at high risk for posttraumatic epilepsy (PTE).
Design: Open-label, nonrandomized phase 2 study with 2 arms comparing levetiracetam treatment vs observation.
Setting: Two level 1 trauma centers.
Patients: A total of 422 participants 6 years or older with TBI who have a 20% risk for PTE were screened. Of these participants, 205 (48.6%) were eligible. A total of 126 participants were enrolled: 86 adults and 40 children. A total of 66 participants were in the treatment group (46 adults and 20 children), and a total of 60 participants were in the observation group (40 adults and 20 children). Participants presenting within 8 hours after TBI received treatment, and those presenting more than 8 to 24 hours after TBI did not.
Intervention: Treatment with levetiracetam (55 mg/kg/d) for 30 days starting within 8 hours after injury.
Main outcome measures: Number of adverse events, mood score, number of infections, trough level of levetiracetam, and PTE.
Results: Of the 66 participants treated with levetiracetam, 2 (3%) stopped treatment owing to toxicity (somnolence). The most common adverse events were fatigue, headache, and somnolence. Mood scores and number of infections did not differ between the treatment and observation groups. Mean trough levels of levetiracetam on days 2 to 30 ranged from 19.6 to 26.7 μg/mL. At 2 years, 13 of 86 adults (15.1%) and 1 of 40 children (2.5%) developed PTE. At 2 years, 5 of 46 treated adults (10.9%) and 8 of 40 untreated adults (20.0%) developed PTE (relative risk, 0.47; P=.18).
Conclusion: Treatment with 55 mg/kg/d of levetiracetam (a dose with an antiepileptogenic effect on animals) for patients with TBI at risk for PTE is safe and well tolerated, with plasma levels similar to those in animal studies. The findings support further evaluation of levetiracetam treatment for the prevention of PTE.
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