Clinical trial NCT00376766: Clinical Trial : TROCC (Quick Oral Treatment of Cluster Epileptic Seizures)
Official title: Rapid Oral Treatment of Cluster Epileptic Seizures. Efficacy Assessment of Levetiracetam in Cluster Seizures.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Epilepsy
Drug Resistant
Keywords: Cluster seizure
seizure clustering
repetitive seizure
Drug resistant epilepsy
Levetiracetam
keppra
Lead sponsor: University Hospital, Grenoble
Sponsor class: OTHER
Collaborators: name: Institut National de la Santé Et de la Recherche Médicale, France
name: UCB Pharma
First posted: 2006-09-15
Enrollment: 112
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a double blind, placebo controlled, add-on clinical trial, of levetiracetam efficacy and safety, in epilepsy cluster seizure.

Efficacy is evaluated in the range of 2 to 24 hours after taking the tablet. If the patient has a seizure during this interval, he is considered as a non-respondent patient.

Detailed description: Seizure clustering has been defined as a series of unusual frequency of seizures with return to baseline between events. The most common definition of cluster seizure is three seizures per 24 hours.

The usual treatment of cluster seizure is benzodiazepin. This is recognized efficient therapy but has many side effects. Thus it is important to develop as an new therapeutic to improve patient care. Levetiracetam is an antiepileptic drug used in addition to other antiepileptic drugs with less side effects than benzodiazepin.

The aim of this study is to evaluate the effectiveness and safety of levetiracetam in epilepsy cluster seizure.

This is a double blind, placebo controlled, add-on clinical trial with two phases :

Phase 1 : Double blind phase during 24 hours (H0 to H24). After consent signature and randomization, the patient takes two tablets of levetiracetam or placebo. If the patient has a seizure between H3 and H24, he is considered as a non-respondent patient. If there is a risk of rapid evolution to an statue epilepticus, the investigator can break the blind and adapt the patient treatment accordingly.

Phase 2 : This is an open phase after H24. this phase consists of breaking the blind with free adaption of the therapy by the investigator, and patients follow-up during 1 month.

The randomization is stratify by center. The size of randomization blocks is random because of the systematic breaking blind after 24 hours.

Eligibility criteria: Inclusion Criteria:

* Age from 18 to 65
* Drug resistant epilepsy, partial seizure
* Epilepsy diagnosed for more than 2 years
* Epilepsy treated for more than 1 year with no change of treatment in the month before the enrolment
* Onset of cluster seizure in the 24 hours before enrolment
* For women : effective contraception
* Affiliation to the French social security

Exclusion Criteria:

* Inability to tolerate levetiracetam, likely poor compliance
* Patient taking antiepileptic treatment (benzodiazepine) in addition to current treatment during the last 48h00.
* Patient taking 1g/day of levetiracetam with Creatinin clearance \< 50ml/min
* Patient taking 2g/day of levetiracetam with Creatinin clearance \< 80ml/min
* Patient taking more than 2g/day of levetiracetam
* Hepatic or cardiovascular pathology
* Progressive psychiatric pathology
* Degenerative neurologic disease
* Cluster seizure due to an acute symptomatic reason
* Disorder of consciousness
* Suspicion of status epilepticus or rapid evolution to status epilepticus
* Suspicion of psychogenic nonepileptic seizure
* Pregnant woman or nursing woman
* Suicidal thoughts
* Incapacity to give consent, minor patient

Primary outcomes:
measure: Ratio of patients who are free of seizure between H3 and H24 in both groups.
Secondary outcomes:
measure: Items 1,2,3 of the Clinical Global Impression scale.
measure: Side effects during the study.
measure: Time between H0 and the last seizure.
measure: Type and ratio of epileptic fit between H0 and H24.
measure: Number of seizures occured between H3 and H10, H10 and H17, H17 and H24, corresponding to the half-time of the treatment (7 hours).
measure: Description of therapeutic adaptation at 1 month after patient enrolment.
Other outcomes:
Locations:
city: Nice
country: France
facility: Neurology department
state: Alpes de Haute provence
city: Tain l'Hermitage
country: France
facility: Etablissement la Teppe
state: Drome
city: Grenoble
country: France
facility: Neurology department
state: Isere
city: St Etienne
country: France
facility: Neurology department
state: Loire
city: Lille
country: France
facility: Neurology department
state: Nord
city: Clermont-Ferrand
country: France
facility: Neurology department
state: Puy de Dome
city: Lyon
country: France
facility: Neurology department
state: Rhone
city: Chambery
country: France
facility: Neurology Department
state: Savoie
city: Nancy
country: France
facility: Neurology department
city: Strasbourg
country: France
facility: Neurology department
Study officials:
affiliation: Central Hospital, Nancy, France
name: Louis Maillard, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital of Strasbourg
name: Serge CHASSAGNON, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital of Strasbourg
name: Cecile SABOURY, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital of Strasbourg
name: Edouard HIRSH, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital of Lille
name: William SZHURAJ, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital of Lille
name: Philippe DERAMBURE, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: La Teppe Institution
name: Jerome PETIT, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: Regional Hospital of Chambery
name: Vincent TAREL, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital, Clermont-Ferrand
name: Dominique ROSENBERG, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital of Lyon
name: Helene CATENOIX, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital of Lyon
name: Philippe RYVELIN, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital of St Etienne
name: Philippe CONVERS, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital of Nice
name: Pierre THOMAS, Dr
role: PRINCIPAL_INVESTIGATOR
References:
citation: Haut SR, Shinnar S, Moshe SL. Seizure clustering: risks and outcomes. Epilepsia. 2005 Jan;46(1):146-9. doi: 10.1111/j.0013-9580.2005.29004.x.
citation: Dreifuss FE, Rosman NP, Cloyd JC, Pellock JM, Kuzniecky RI, Lo WD, Matsuo F, Sharp GB, Conry JA, Bergen DC, Bell WE. A comparison of rectal diazepam gel and placebo for acute repetitive seizures. N Engl J Med. 1998 Jun 25;338(26):1869-75. doi: 10.1056/NEJM199806253382602.
citation: Mitchell WG, Conry JA, Crumrine PK, Kriel RL, Cereghino JJ, Groves L, Rosenfeld WE. An open-label study of repeated use of diazepam rectal gel (Diastat) for episodes of acute breakthrough seizures and clusters: safety, efficacy, and tolerance. North American Diastat Group. Epilepsia. 1999 Nov;40(11):1610-7. doi: 10.1111/j.1528-1157.1999.tb02047.x.
citation: Shorvon SD, Lowenthal A, Janz D, Bielen E, Loiseau P. Multicenter double-blind, randomized, placebo-controlled trial of levetiracetam as add-on therapy in patients with refractory partial seizures. European Levetiracetam Study Group. Epilepsia. 2000 Sep;41(9):1179-86. doi: 10.1111/j.1528-1157.2000.tb00323.x.
citation: Cereghino JJ, Biton V, Abou-Khalil B, Dreifuss F, Gauer LJ, Leppik I. Levetiracetam for partial seizures: results of a double-blind, randomized clinical trial. Neurology. 2000 Jul 25;55(2):236-42. doi: 10.1212/wnl.55.2.236.