Levetiracetam Versus Carbamazepine in Post-Stroke Late Onset Crisis "EpIc"

Recruiting

Phase 3 Results N/A

Trial Description

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.

Detailed 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.

Conditions

Interventions

  • Levetiracetam (Levetiracetam)Drug
    Other Names: Keppra
    Intervention Desc: Levetiracetam tablets 250-500 mg. The drug dosage will be up-titrated from 250 mg bid in the first 2 weeks to 500 mg bid during the rest of the treatment period. The dosage can be incremented until 1500 mg bid, at Investigator judgement if crisis continue, or it can be reduced in case of adverse events
    ARM 1: Kind: Experimental
    Label: LEV
    Description: Levetiracetam
  • Carbamazepine Drug
    Intervention Desc: Carbamazepina tablets 200 mg. The drug dosage will be up-titrated from 100 mg die in the first 3 days to 100 mg bid during days 4 to 7, to 200 mg bid in the 2nd week, to 300 mg bid during the rest of the treatment period. The dosage can be incremented until 800 mg bid, at Investigator judgement if crisis continue, or it can be reduced in case of adverse events
    ARM 1: Kind: Experimental
    Label: CAR
    Description: Carbamazepina

Trial Design

  • Allocation: Randomized
  • Masking: Open Label
  • Purpose: Treatment
  • Intervention: Parallel Assignment

Patient Involvement

EEG at baseline and one year follow-up; cognitive function and quality of life evaluation at one year follow-up; and compare seizure frequency at one year follow-up.

Outcomes

Type Measure Time Frame Safety Issue
Primary Number of patients free from post stroke recurrent crisis (seizures).
Secondary To compare retention time of levetiracetam vs carbamazepine since first intake throughout treatment period; to compare time to second seizure in both treatments; to evaluate differences in cognitive function and in quality of life in levetiracetam and carbamazepine patients having post-stroke seizures at the end of treatment period; evaluate EEG changes as compared with baseline with that obtained at the end of treatment period; to compare seizure frequency in levetiracetam and carbamazepine groups throughout treatment period; to evaluate the safety of levetiracetam versus carbamazepine throughout the treatment period.
Primary number of patients free from post stroke recurrent crisis one year No
Secondary To compare retention time of LEV vs CBZ since first intake throughout treatment period one year No
Secondary To compare time to second seizure in both treatments. one year No
Secondary To evaluate differences in cognitive function and in quality of life in levetiracetam and carbamazepine patients having post-stroke seizures at the end of treatment period one year No
Secondary evaluate EEG changes as compared with baseline with that obtained at the end of treatment period one year No
Secondary To compare seizure frequency in levetiracetam and carbamazepine groups throughout treatment period one year No
Secondary To evaluate the safety of levetiracetam versus carbamazepine throughout the treatment period one year Yes

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