Epilepsia
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Randomized Controlled Trial Multicenter Study
A double-blind, randomized, placebo-controlled trial of a diazepam auto-injector administered by caregivers to patients with epilepsy who require intermittent intervention for acute repetitive seizures.
A diazepam auto-injector (AI) has been developed for intramuscular administration to treat acute repetitive seizures (ARS). The objective of this study was to evaluate the efficacy and safety of the diazepam AI when administered by caregivers to control an episode of ARS. ⋯ The diazepam AI was significantly more effective than placebo AI at delaying the next seizure or rescue. Secondary efficacy end points were generally supportive of the primary outcome. Diazepam AI administered by trained caregivers was effective for the treatment of ARS and was well-tolerated, with a safety profile similar to placebo.
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Randomized Controlled Trial
Lessons from the RAMPART study--and which is the best route of administration of benzodiazepines in status epilepticus.
Early treatment of prolonged seizures with benzodiazepines given intravenously by paramedics in the prehospital setting had been shown to be associated with improved outcomes, but the comparative efficacy and safety of an intramuscular (IM) route, which is faster and consistently achievable, was previously unknown. RAMPART (the Rapid Anticonvulsant Medication Prior to Arrival Trial) was a double-blind randomized clinical trial to determine if the efficacy of intramuscular (IM) midazolam is noninferior by a margin of 10% to that of intravenous (IV) lorazepam in patients treated by paramedics for status epilepticus (SE). ⋯ Patients treated with IM midazolam were more likely to have stopped seizing at emergency department (ED) arrival, without emergency medical services (EMS) rescue therapy, and were less likely to require any hospitalization or admission to an intensive care unit. Lessons from the RAMPART study's findings and potential implications on clinical practice, on the potential role of other routes of administration, on the effect of timing of interventions, and on future clinical trials are discussed.
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Randomized Controlled Trial
Efficacy and safety of adjunctive perampanel for the treatment of refractory partial seizures: a pooled analysis of three phase III studies.
Three phase III studies (304 [ClinicalTrials.gov identifier: NCT00699972], 305 [NCT00699582], 306 [NCT00700310]) evaluated perampanel, an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist, as adjunctive therapy for refractory partial seizures. We report post hoc analyses of pooled study data by randomized dose. ⋯ Perampanel reduced partial seizure frequency and improved responder rates compared with placebo, with an acceptable tolerability profile.
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Randomized Controlled Trial
A randomized phase III trial of adjunctive zonisamide in pediatric patients with partial epilepsy.
To assess the efficacy and safety/tolerability of adjunctive zonisamide treatment in pediatric patients with partial epilepsy. ⋯ Adjunctive zonisamide treatment was shown to be effective and well tolerated in pediatric patients with partial epilepsy. No new or unexpected safety findings emerged.
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Randomized Controlled Trial Multicenter Study
Concentration-effect relationships with perampanel in patients with pharmacoresistant partial-onset seizures.
Although there is a general paucity of published pharmacokinetic (PK) data for new antiepileptic drugs (AEDs), PK analyses of pooled data from clinical studies of perampanel have recently been presented. We present PK/pharmacodynamic (PD) analyses of pooled data from phase III studies of perampanel describing efficacy and safety as a function of exposure, in order to determine whether a predictable concentration-effect relationship exists for perampanel efficacy and/or adverse events (AEs). The effects of concomitant enzyme-inducing AEDs (EIAEDs) and non-enzyme-inducing AEDs on the exposure, efficacy, and safety of perampanel are also considered. ⋯ PK and PD analyses have played a pivotal role in the clinical development of perampanel as an adjunctive treatment for pharmacoresistant partial-onset seizures. Phase III data suggest that a significant relationship exists between increases in perampanel plasma concentration (i.e., systemic exposure) and reductions in seizure frequency. In addition, increases in perampanel plasma concentration may potentially be associated with increases in AE rates. The model-predicted concentration-safety profile of perampanel does not appear to be affected by patient age, gender, or ethnicity. Although concomitant EIAEDs may influence perampanel PK, they do not appear to alter the relationship between perampanel plasma concentration and seizure frequency. Understanding these relationships between perampanel plasma concentration and clinical response will be valuable in utilizing this novel AED.