Results of Phase 2 Safety and Feasibility Study of Treatment With Levetiracetam for Prevention of Posttraumatic Epilepsy
| Autor: | Claude Nogay, Zachary Levine, Jianping He, Shireen M. Atabaki, Steven J. Soldin, Robert McCarter, Tammy Tsuchida, Daniel Herr, JoAnne E Natale, Fabian Sandoval, Stacey Trzcinski, Pavel Klein, Phillip L. Pearl, John N. van den Anker |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Adult
Male Pediatrics medicine.medical_specialty Levetiracetam Time Factors Adolescent Poison control Article Young Adult Arts and Humanities (miscellaneous) Tandem Mass Spectrometry medicine Humans Adverse effect Child Chromatography High Pressure Liquid Aged Aged 80 and over Epilepsy business.industry Age Factors Middle Aged Piracetam Survival Analysis Clinical trial Tolerability Anesthesia Relative risk Brain Injuries Phenytoin Trough level Feasibility Studies Patient Compliance Anticonvulsants Female Neurology (clinical) medicine.symptom business Somnolence medicine.drug Follow-Up Studies |
| Popis: | 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. Trial registration clinicaltrials.gov Identifier: NCT01463033. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|