Levetiracetam Versus Carbamazepine in Post-Stroke Late Onset Crisis

NCT ID: NCT00542802

Last Updated: 2008-05-30

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 630 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-09-30
• Study Completion Date: 2009-06-30

Brief 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.

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

Epileptic Seizures; Stroke

Keywords

post stroke epileptic late onset seizures

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

LEV

Levetiracetam

Group Type: EXPERIMENTAL

Levetiracetam

Intervention Type: DRUG

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

CAR

Carbamazepina

Group Type: ACTIVE_COMPARATOR

Carbamazepine

Intervention Type: DRUG

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

Interventions

Levetiracetam

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

Intervention Type: DRUG

Carbamazepine

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Patients having a stroke (ischemic and haemorrhagic) showing (one) subsequent seizure 14 days up to 3 years after stroke
• Patients has signed the informed consent form
• Aged ≥ 18 years

Exclusion Criteria

• Severe stroke patients with Rankin scale > 3
• Patients with a life expectancy of < 12 months
• Patients screened more than 15 days after first seizure
• Patients with a diagnosed epilepsy
• Patients with clear evidence of myoclonic seizures
• Patients with contraindication to levetiracetam and carbamazepine use
• Patients presenting epileptic status at onset
• Patients having a MMSE <24
• Patients having a seizure before stroke
• Patients taking any AED 4 weeks prior to randomisation in the study
• Patients showing dysphagia after stroke not able to swallow tablets.
• Patients with a low compliance for the study
• Pregnant women, lactating or sexually active women with childbearing potential who are not using a medically accepted birth control method.
• Allergy or intolerance to pyrrolidine derivatives and/or tablet excipients or to carbamazepine derivates and /or tablet excipients
• Patients involved in another clinical trial 30 days prior randomization
• Patients with any tumour
• Patients with previous traumatic brain accident resulting in impairment of consciousness.
• Patients for whom it is not possible to assess seizure onset

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Scienze Neurologiche Ospedaliere

OTHER

Sponsor Role: lead

Responsible Party

Scienze Neurologiche Ospedaliere

Principal Investigators

domenico consoli, doctor

Role: PRINCIPAL_INVESTIGATOR

Ospedale Civile Vibo Valentia

Locations

Ospedale S. Giacomo

Novi Ligure, AL, Italy

Site Status: NOT_YET_RECRUITING

Ospedale S. Croce E Carle

Cuneo, CN, Italy

Site Status: NOT_YET_RECRUITING

Ospedale S. Martino

Genova, GE, Italy

Site Status: RECRUITING

Istituto Clinico Humanitas

Rozzano, MI, Italy

Site Status: RECRUITING

USL 2 Ospedale B.G. Villa

Città della Pieve, PG, Italy

Site Status: NOT_YET_RECRUITING

Ospedale Civile San Giovanni Battista di Foligno

Foligno, PG, Italy

Site Status: RECRUITING

Ospedale Santa Maria della Misericordia

Sant'Andrea Delle Fratte, PG, Italy

Site Status: NOT_YET_RECRUITING

Istituto Neurologico C. Mondino

Pavia, PV, Italy

Site Status: NOT_YET_RECRUITING

Ospedale Guzzardi

Vittoria, RG, Italy

Site Status: RECRUITING

Ospedale Di Portogruaro

Portogruaro, VE, Italy

Site Status: RECRUITING

Ospedale Civile

Vibo Valentia, VV, Italy

Site Status: RECRUITING

Policlinico Umberto I

Ancona, , Italy

Site Status: NOT_YET_RECRUITING

Ospedale A. Perrino

Brindisi, , Italy

Site Status: RECRUITING

Ospedale Cannizzaro

Catania, , Italy

Site Status: NOT_YET_RECRUITING

Ospedale San Martino

Genova, , Italy

Site Status: RECRUITING

Ospedale Civile Imperia ASL 1

Imperia, , Italy

Site Status: RECRUITING

Ospedale A. Cardarelli-

Napoli, , Italy

Site Status: RECRUITING

Ospedale Cardarelli

Napoli, , Italy

Site Status: NOT_YET_RECRUITING

Ospedale Civico

Palermo, , Italy

Site Status: NOT_YET_RECRUITING

Osp. Guglielmo da saliceto

Piacenza, , Italy

Site Status: RECRUITING

Arcispedale S. Maria Nuova

Reggio Emilia, , Italy

Site Status: RECRUITING

Ospedale SS. Annunziata - Ospedale Civile

Taranto, , Italy

Site Status: RECRUITING

Ospedale Molinette-Università di Torino

Torino, , Italy

Site Status: RECRUITING

Azienda Ospedaliera Universitaria Trieste

Trieste, , Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Domenico Consoli, Doctor

Role: CONTACT

Email: domco@tiscali.it

Sara Papetti

Role: CONTACT

Phone: 0382 530676

Email: spapetti@gbpharmaservices.it

Facility Contacts

Anna Cavallini, doctor

Role: primary

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Other Identifiers

EpIc 1151

Identifier Type: -

Identifier Source: org_study_id