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

ABSTRACT: 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).Open-label, nonrandomized phase 2 study with 2 arms comparing levetiracetam treatment vs observation.Two level 1 trauma centers.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.Treatment with levetiracetam (55 mg/kg/d) for 30 days starting within 8 hours after injury.Number of adverse events, mood score, number of infections, trough level of levetiracetam, and PTE.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 ?g/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).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.clinicaltrials.gov Identifier: NCT01463033.

SUBMITTER: Klein P

PROVIDER: S-EPMC4798941 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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

Klein Pavel P Herr Daniel D Pearl Phillip L PL Natale JoAnne J Levine Zachary Z Nogay Claude C Sandoval Fabian F Trzcinski Stacey S Atabaki Shireen M SM Tsuchida Tammy T van den Anker John J Soldin Steven J SJ He Jianping J McCarter Robert R

Archives of neurology 20121001 10

<h4>Objectives</h4>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).<h4>Design</h4>Open-label, nonrandomized phase 2 study with 2 arms comparing levetiracetam treatment vs observation.<h4>Setting</h4>Two level 1 trauma centers.<h4>Patients</h4>A total of 422 participants 6 years or older with TBI who have a 20% risk for PTE we ...[more]

PMID: 22777131

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Project description:ObjectiveTo evaluate the efficacy, safety and economics of levetiracetam (LEV) for epilepsy.Materials and methodsPubMed, Scopus, the Cochrane Library, OpenGrey.eu and ClinicalTrials.gov were searched for systematic reviews (SRs), meta-analyses, randomized controlled trials (RCTs), observational studies, case reports and economic studies published from January 2007 to April 2018. We used a bubble plot to graphically display information of included studies and conducted meta-analyses to quantitatively synthesize the evidence.ResultsA total of 14,803 records were obtained. We included 30 SRs/meta-analyses, 34 RCTs, 18 observational studies, 58 case reports and 2 economic studies after the screening process. The included SRs enrolled patients with pediatric epilepsy, epilepsy in pregnancy, focal epilepsy, generalized epilepsy and refractory focal epilepsy. Meta-analysis of the included RCTs indicated that LEV was as effective as carbamazepine (CBZ; treatment for 6 months: 58.9% vs 64.8%, OR=0.76, 95% CI: 0.50-1.16; 12 months: 54.9% vs 55.5%, OR=1.24, 95% CI: 0.79-1.93), oxcarbazepine (57.7% vs 59.8%, OR=1.34, 95% CI: 0.34-5.23), phenobarbital (50.0% vs 50.9%, OR=1.20, 95% CI: 0.51-2.82) and lamotrigine (LTG; 61.5% vs 57.7%, OR=1.22, 95% CI: 0.90-1.66). SRs and observational studies indicated a low malformation rate and intrauterine death rate for pregnant women, as well as low risk of cognitive side effects. But psychiatric and behavioral side effects could not be ruled out. LEV decreased discontinuation due to adverse events compared with CBZ (OR=0.52, 95% CI: 0.41-0.65), while no difference was found when LEV was compared with placebo and LTG. Two cost-effectiveness evaluations for refractory epilepsy with decision-tree model showed US$ 76.18 per seizure-free day gained in Canada and US$ 44 per seizure-free day gained in Korea.ConclusionLEV is as effective as CBZ, oxcarbazepine, phenobarbital and LTG and has an advantage for pregnant women and in cognitive functions. Limited evidence supports its cost-effectiveness.Registered numberPROSPERO (No CRD 42017069367).

Project description:Importance:More than half of infants with new-onset epilepsy have electroencephalographic and clinical features that do not conform to known electroclinical syndromes (ie, nonsyndromic epilepsy). Levetiracetam and phenobarbital are the most commonly prescribed medications for epilepsy in infants, but their comparative effectiveness is unknown. Objective:To compare the effectiveness of levetiracetam vs phenobarbital for nonsyndromic infantile epilepsy. Design, Setting, and Participants:The Early Life Epilepsy Study-a prospective, multicenter, observational cohort study conducted from March 1, 2012, to April 30, 2015, in 17 US medical centers-enrolled infants with nonsyndromic epilepsy and a first afebrile seizure between 1 month and 1 year of age. Exposures:Use of levetiracetam or phenobarbital as initial monotherapy within 1 year of the first seizure. Main Outcomes and Measures:The binary outcome was freedom from monotherapy failure at 6 months, defined as no second prescribed antiepileptic medication and freedom from seizures beginning within 3 months of initiation of treatment. Outcomes were adjusted for demographics, epilepsy characteristics, and neurologic history, as well as for observable selection bias using propensity score weighting and for within-center correlation using generalized estimating equations. Results:Of the 155 infants in the study (81 girls and 74 boys; median age, 4.7 months [interquartile range, 3.0-7.1 months]), those treated with levetiracetam (n?=?117) were older at the time of the first seizure than those treated with phenobarbital (n?=?38) (median age, 5.2 months [interquartile range, 3.5-8.2 months] vs 3.0 months [interquartile range, 2.0-4.4 months]; P?<?.001). There were no other significant bivariate differences. Infants treated with levetiracetam were free from monotherapy failure more often than those treated with phenobarbital (47 [40.2%] vs 6 [15.8%]; P?=?.01). The superiority of levetiracetam over phenobarbital persisted after adjusting for covariates, observable selection bias, and within-center correlation (odds ratio, 4.2; 95% CI, 1.1-16; number needed to treat, 3.5 [95% CI, 1.7-60]). Conclusions and Relevance:Levetiracetam may have superior effectiveness compared with phenobarbital for initial monotherapy of nonsyndromic epilepsy in infants. If 100 infants who received phenobarbital were instead treated with levetiracetam, 44 would be free from monotherapy failure instead of 16 by the estimates in this study. Randomized clinical trials are necessary to confirm these findings.

Project description:ObjectivesPatient involvement in safety improvement is a developing area of research. The aim of this study was to investigate the feasibility of a patient feedback on safety intervention in primary care. Specifically, the intervention acceptability, fidelity, implementation enablers and barriers, scalability, and process of systematically collecting safety data were examined.Design, setting and participantsMixed-methods feasibility trial with six purposively selected Australian primary care practices.InterventionThe intervention comprised an iterative process with a cycle of measurement, learning, feedback, action planning and implementation period of 6 months.Primary and secondary outcomesQualitative and quantitative data relating to feasibility measures (acceptability, fidelity, enablers, barriers, scalability and process of collecting safety data) were collected and analysed.ResultsA total of n=1750 patients provided feedback on safety. There was a statistically significant increase in mean patient safety scores indicating improved safety (4.30-4.37, p=0.002). Staff deemed the intervention acceptable, with minor recommendations for improvement. Intervention fidelity was high and implementation enablers were attributed to the intervention structure and framework, use of intuitive problem-solving approaches, and multidisciplinary team involvement. Practice-based safety interventions resulted in sustainable and measurable changes to systems for safety, such as increased access to care and improved patient information accuracy.ConclusionsThe findings indicate that this innovative patient feedback on safety intervention is feasible for scale-up to a larger effectiveness trial and further spread into policy and practice. This intervention complements existing safety improvement strategies and activities, and integrates into current patient feedback service requirements for Australian primary care. Further research is needed to examine the intervention effects on safety incident reduction.

Project description:IntroductionMost smoking quit attempts end in relapse, and interventions focused on relapse prevention are lacking. Helpers Stay Quit (HSQ) is a novel behavioral relapse prevention intervention that teaches newly abstinent smokers to offer a "helping conversation" (HC) to help others quit tobacco.MethodsPre-post intervention feasibility study with state quitline participants ≥14 days abstinent. Measures at baseline, 3 months, and 6 months included smoking status, offering HCs, and cessation self-efficacy. Primary outcomes: self-reported 7-day point prevalence abstinence; offering HCs. Cox models explored association of HCs with relapse. Preliminary effects analysis using propensity score matching compared 30-day abstinence of quitline clients with study sample at 7 months.ResultsParticipants (N = 104) were as follows: mean age of 53 years (SD 13.9 years), 48.1% male, mean of cigarettes smoked/day of 16.2 (SD 9.7). Compared with participants who remained abstinent (n = 82), relapsers (n = 22) had fewer HCs over 6 months (2.6 vs 7.2; 95% confidence interval [CI]: 1.4, 7.8, p = .006). Using adjusted Cox regression, the hazard ratio of relapse for each HC was 0.85 (95% CI: 0.74, 0.99, p = .03). Compared with a matched sample of quitline clients not exposed to HSQ, study participants were 49% more likely to report 30-day abstinence at 7-month quitline follow-up (95% CI: 40%, 59%, p < .0001).ConclusionsHSQ, delivered to newly abstinent smokers who received standard quitline treatment, was associated with less self-reported relapse. These promising preliminary study results warrant further research to evaluate HSQ as a novel behavioral intervention to prevent smoking relapse.ImplicationsTo date, behavioral interventions for smoking relapse prevention that teach abstainers cessation skills to apply to themselves have not shown effectiveness. This feasibility study examines the preliminary efficacy of a conceptually novel, "help others" behavioral intervention approach for relapse prevention in newly abstinent smokers recruited from a state quitline. HSQ teaches the newly abstinent smoker communication and listening skills to encourage other smokers in their personal social network to quit. Exploratory analysis using propensity score matching suggests that participants exposed to HSQ were significantly more likely to self-report 30-day abstinence at quitline 7-month follow-up than other quitline clients.

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

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

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