Levetiracetam Versus Carbamazepine in Post-Stroke Late Onset Crisis
Summary
The principal purpose of the study is to determine the efficacy and safety of Levetiracetam versus Carbamazepine, intended as the number of patients free from crisis during the whole period of treatment, in patients affected by post stroke late onset crisis.
Description
Stroke is the most common cause of seizures in the elderly and seizures are among the most common sequelae of stroke.
About 10% of patients experience seizures since stroke onset up to several years (Silverman 2002). Arbitrarly a cut point of 2 weeks divide early seizures from late seizures (Honey 2000, Olofson 2000, Berger 1989).Late occurrence of late seizure appears to carry a high risk for epilepsy (Wilmore 1990).
The risk of epilepsy in some patients with a single stroke-related seizure is high enough to justify starting an anticonvulsant therapy before a second seizure occurs(Labovitz 2003).
Levetiracetam (S-α-ethil-2-oxo-pyrrolidine acetamide) is S-enantiomer of a pyrrolidine derivative and is unrelated to any other AED and has a unique preclinical and clinical profile (Gower et al 1992).
Levetiracetam (LEV) binds with a stereospecific binding site in the CNS that is saturable and reversible (Noyer 1995). This site actually known as LBS Levetiracetam Binding Site) is unique and do not correspond to any known receptor or channel that might be involved in neuroexcitability (Gillard 2003).
LEV selectively inhibits N-type Ca2 channels of CA1 pyramidal hyppocampal neurons (Lukyanetz et a 2002) and, despite of not having any activity on GABA-gated currents, it shows a potent ability to reverse the inhibitory effects of the negative allosteric modulators zinc and β-carbolines on both GABAA and glycine receptor mediated responses(Rigo et al. 2002).
LEV has no effects on normal neurons (Birnstiel et al.1997) LEV as other AEDs has effect in decreasing repetitive neuronal firing, but only LEV reduces the number of cells firing synchronously (amplitude) of the evoked PS(Margineau and Klitgaard 2000).
The efficacy profile of the drug has been established through three pivotal randomized double blind, placebo controlled, parallel studies on 904 patients suffering from partial seizures secondarily or not generalised that were not well controlled by previous treatment (Shorvon et al. 2000; Ben-Menachem et al. 2000; Cereghino et al. 2000).In these three studies LEV showed a significant reduction of seizure frequency. A pooled analysis of the results from these three studies supports a dose-response effect for levetiracetam: responder rates were 28.5, 34.3 and 41.3 % for patients treated with levetiracetam 1000, 2000, 3000 mg/day respectively, as compared with 13.1% for placebo group. The respective values for complete seizure freedom were 4.7, 6.3, 8.6 and 0.8%(Privitera 2002, Boon et al, 2002).
In a review of data for 1422 patients treated with levetiracetam, 38.6% of patients experienced a ≥ 50% reduction in seizure frequency and 20% experienced a reduction of ≥ 75%. The present study is not blinded because one of the purposes with the study has been to mimic daily clinical practice as close as possible.
Study Design
Allocation: Randomized, Control: Active Control, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Conditions
Epileptic Seizures
Intervention
Levetiracetam, Carbamazepine
Location
Ospedale S. Giacomo
Novi Ligure
AL
Italy
15057
Status
Recruiting
Source
Scienze Neurologiche Ospedaliere
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00542802
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Carbamazepine
An anticonvulsant used to control grand mal and psychomotor or focal seizures. Its mode of action is not fully understood, but some of its actions resemble those of PHENYTOIN; although there is little chemical resemblance between the two compounds, their three-dimensional structure is similar.
Epilepsy, Generalized
Recurrent conditions characterized by epileptic seizures which arise diffusely and simultaneously from both hemispheres of the brain. Classification is generally based upon motor manifestations of the seizure (e.g., convulsive, nonconvulsive, akinetic, atonic, etc.) or etiology (e.g., idiopathic, cryptogenic, and symptomatic). (From Mayo Clin Proc, 1996 Apr;71(4):405-14)
Clonazepam
An anticonvulsant used for several types of seizures, including myotonic or atonic seizures, photosensitive epilepsy, and absence seizures, although tolerance may develop. It is seldom effective in generalized tonic-clonic or partial seizures. The mechanism of action appears to involve the enhancement of GAMMA-AMINOBUTYRIC ACID receptor responses.
Seizures, Febrile
Seizures that occur during a febrile episode. It is a common condition, affecting 2-5% of children aged 3 months to five years. An autosomal dominant pattern of inheritance has been identified in some families. The majority are simple febrile seizures (generally defined as generalized onset, single seizures with a duration of less than 30 minutes). Complex febrile seizures are characterized by focal onset, duration greater than 30 minutes, and/or more than one seizure in a 24 hour period. The likelihood of developing epilepsy (i.e., a nonfebrile seizure disorder) following simple febrile seizures is low. Complex febrile seizures are associated with a moderately increased incidence of epilepsy. (From Menkes, Textbook of Child Neurology, 5th ed, p784)
Alcohol Withdrawal Seizures
A condition where seizures occur in association with ethanol abuse (ALCOHOLISM) without other identifiable causes. Seizures usually occur within the first 6-48 hours after the cessation of alcohol intake, but may occur during periods of alcohol intoxication. Single generalized tonic-clonic motor seizures are the most common subtype, however, STATUS EPILEPTICUS may occur. (Adams et al., Principles of Neurology, 6th ed, p1174)
Clinical Trials
An Open Label Study of Levetiracetam in Japanese Pediatric Patients With Partial Seizures
Objective of the First Period: To evaluate the efficacy of levetiracetam dry syrup at doses up to a maximum of 60 mg/kg/day or 3000 mg/day used as an adjunctive therapy in Japanese pediatr...
Prevention of Post-traumatic Seizures With Levetiracetam
Post-traumatic seizures can appear frequently after a severe traumatic brain injury. Two types of seizures are usually identified: early seizures during the week following the trauma and l...
Safety Study Of Intravenous Levetiracetam
The test article for this study is levetiracetam (Keppra, which is commercially available. Keppra is indicated for use as adjunctive therapy in the treatment of partial onset seizure disor...
Pharmacokinetic and Safety Trial of Intravenous Levetiracetam in the Treatment of Neonatal Seizures
The hypothesis is that a loading dose of 20 mg/kg and a maintenance dose of 5 mg/kg of Levetiracetam is going to be safe and effective in the treatment of seizures in neonates.
Bridging Study of L059 (Levetiracetam) in Patients With Epilepsy by Double Blind Method
Double-blind, randomized, placebo-controlled, multi center trial to evaluate the efficacy and safety of levetiracetam as adjunctive treatment in adult Japanese epileptic subjects with part...
PubMed Articles
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