Results of phase 2 safety and feasibility study of treatment with levetiracetam for prevention of posttraumatic epilepsy

Pavel Klein, Daniel Herr, Phillip L. Pearl, JoAnne E 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

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Abstract

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 adultsand20children). Participants presenting within8hours 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. Trial Registration: clinicaltrials.gov Identifier: NCT01463033

Original languageEnglish (US)
Pages (from-to)1290-1295
Number of pages6
JournalArchives of Neurology
Volume69
Issue number10
DOIs
StatePublished - Oct 2012
Externally publishedYes

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etiracetam
Feasibility Studies
Epilepsy
Safety
Therapeutics
Observation
Trauma Centers

ASJC Scopus subject areas

  • Clinical Neurology
  • Arts and Humanities (miscellaneous)

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Results of phase 2 safety and feasibility study of treatment with levetiracetam for prevention of posttraumatic epilepsy. / Klein, Pavel; Herr, Daniel; Pearl, Phillip L.; Natale, JoAnne E; Levine, Zachary; Nogay, Claude; Sandoval, Fabian; Trzcinski, Stacey; Atabaki, Shireen M.; Tsuchida, Tammy; Van Den Anker, John; Soldin, Steven J.; He, Jianping; McCarter, Robert.

In: Archives of Neurology, Vol. 69, No. 10, 10.2012, p. 1290-1295.

Research output: Contribution to journalArticle

Klein, P, Herr, D, Pearl, PL, Natale, JE, Levine, Z, Nogay, C, Sandoval, F, Trzcinski, S, Atabaki, SM, Tsuchida, T, Van Den Anker, J, Soldin, SJ, He, J & McCarter, R 2012, 'Results of phase 2 safety and feasibility study of treatment with levetiracetam for prevention of posttraumatic epilepsy', Archives of Neurology, vol. 69, no. 10, pp. 1290-1295. https://doi.org/10.1001/archneurol.2012.445
Klein, Pavel ; Herr, Daniel ; Pearl, Phillip L. ; Natale, JoAnne E ; Levine, Zachary ; Nogay, Claude ; Sandoval, Fabian ; Trzcinski, Stacey ; Atabaki, Shireen M. ; Tsuchida, Tammy ; Van Den Anker, John ; Soldin, Steven J. ; He, Jianping ; McCarter, Robert. / Results of phase 2 safety and feasibility study of treatment with levetiracetam for prevention of posttraumatic epilepsy. In: Archives of Neurology. 2012 ; Vol. 69, No. 10. pp. 1290-1295.
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abstract = "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 adultsand20children). Participants presenting within8hours 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. Trial Registration: clinicaltrials.gov Identifier: NCT01463033",
author = "Pavel Klein and Daniel Herr and Pearl, {Phillip L.} and Natale, {JoAnne E} and Zachary Levine and Claude Nogay and Fabian Sandoval and Stacey Trzcinski and Atabaki, {Shireen M.} and Tammy Tsuchida and {Van Den Anker}, John and Soldin, {Steven J.} and Jianping He and Robert McCarter",
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AU - Klein, Pavel

AU - Herr, Daniel

AU - Pearl, Phillip L.

AU - Natale, JoAnne E

AU - Levine, Zachary

AU - Nogay, Claude

AU - Sandoval, Fabian

AU - Trzcinski, Stacey

AU - Atabaki, Shireen M.

AU - Tsuchida, Tammy

AU - Van Den Anker, John

AU - Soldin, Steven J.

AU - He, Jianping

AU - McCarter, Robert

PY - 2012/10

Y1 - 2012/10

N2 - 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 adultsand20children). Participants presenting within8hours 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. Trial Registration: clinicaltrials.gov Identifier: NCT01463033

AB - 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 adultsand20children). Participants presenting within8hours 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. Trial Registration: clinicaltrials.gov Identifier: NCT01463033

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