The objectives of this multi-centre, double-blind, randomized, 2-parallelgroups study are to investigate the efficacy, safety and tolerability of levetiracetam (LEV) monotherapy 15-60mg/kg/day versus valproic acid (VPA) monotherapy 10-40mg/kg/day in…
ID
Source
Brief title
Condition
- Seizures (incl subtypes)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Retention rate after 52 weeks of treatment comparing LEV versus VPA
Secondary outcome
- Changes in cognitive development and behaviour
- Terminal remission
- Time to withdrawal from study treatment.
- Percentage of patients being seizure-free after 26 and 52 weeks on
antiepileptic drug treatment
- Percentage of patients with >50% seizure reduction (as compared to the last 4
weeks before inclusion) after 52 weeks
- Per epilepsy syndrome: Percentage of patients being seizure-free or with a
seizure reduction of more than 50%
- Incidence of side-effects and interactions
Background summary
Very few antiepileptic drugs (AEDs) are licensed for initial use as monotherapy
in children with newly diagnosed epilepsy. Valproic acid (VPA) is the most
frequently prescribed AED in children with epilepsy. It is effective in a broad
spectrum of different seizure types, but it is related to a number of (serious)
side effects. An efficacious and broad spectrum AED with an improved safety
profile that can be used as monotherapy in children is therefore needed.
Study objective
The objectives of this multi-centre, double-blind, randomized, 2-parallelgroups
study are to investigate the efficacy, safety and tolerability of levetiracetam
(LEV) monotherapy 15-60mg/kg/day versus valproic acid (VPA) monotherapy
10-40mg/kg/day in 200 children aged 2 to 16 years with newly diagnosed epilepsy.
We investigate whether LEV is just as effective as or even more effective than
VPA with less side-effects. If LEV proves to be as effective as VPA with less
side-effects, it might even take over its position as the first choice
antiepileptic drug in children with epilepsy.
Study design
Multi-centre, double-blind, randomized, 2-parallelgroups
Intervention
One group will receive levetiracetam (LEV) monotherapy 15-60mg/kg/day, the
other group valproic acid (VPA) monotherapy 10-40mg/kg/day. Treatment will
start with a low dose and can be increased every 2 weeks until the optimal dose
is reached, i.e. with reduction of seizures or becoming seizure-free with no or
few side-effects. The daily dose will be divided in two equal dosages to be
given in the morning and evening.
Study burden and risks
Subjects will be treated for a maximum of 52 weeks with trial medication.
During the first visit a physical examination will be performed before the
first levetiracetam/valproic acid intake to make sure that all in- and
exclusion criteria are met. This also includes a venapuncture to exclude liver
function disturbances and haematological disorders (standard procedure before
the start of valproic acid). The study includes 5 visits (at 0, 13, 26, 39 and
52 weeks of treatment), and 3 telephone contacts (at 2, 4 and 6 weeks of
treatment). If necessary, other investigations, such as an EEG or CT/MRI scan
can be performed, but these are not required for the study.
Parents/caregiver and/or children will be asked to record all seizures in a
diary. If possible, we also ask the teacher to fill in this diary.
At the start and end of the study, the parents/caregivers and, if applicable,
the child and his/her teacher have to complete questionnaires about cognitive
functioning and behaviour.
Patients aged 6 years or older who are enrolled in Groningen will receive an
extensive neuropsychological assessment at the same time points. This consists
of tests on intelligence, learning and memory, executive functioning, attention
and psychomotor speed, and social cognition (duration approximately 3.5 hours).
Hanzeplein 1
Groningen 9713 GZ
NL
Hanzeplein 1
Groningen 9713 GZ
NL
Listed location countries
Age
Inclusion criteria
- Children of either sex from age 2 until (and including) age 15 years with weight between 13 and 60 kilograms
- New but confident diagnosis of epilepsy made during the last year
- According to the treating physician initiation of antiepileptic medication is indicated
Exclusion criteria
- Weight (corrected for length) >+2SD above average as defined in the *Groeidiagrammen* of TNO, 2010
- Treatable underlying cause of epilepsy (e.g. GLUT1-deficiency syndrome)
- Serious pre-existing behavioural disturbances (according to clinician*s judgment) or serious psychiatric disorders requiring hospitalization or medication
- Uncountable seizures (clusters) or history of convulsive status epilepticus or mitochondrial disease (based on clinical characteristics or laboratory tests)
- Earlier treatment with any other AED for seizures, other than emergency treatment, in the year before inclusion
- Earlier treatment with LEV or VPA for any indication at any time
- Participation in another clinical trial with an investigational drug or device within 12 weeks of inclusion, or at any time during this study
- Known presence or history of allergy to the components of LEV or other pyrrolidine derivates or VPA
- Any known disorder or condition that may interfere with the absorption, distribution, metabolisation or excretion of drugs (e.g. end stage renal disease, patients on dialysis, patients with hepatic disease, etc.)
- Pregnancy or at risk of becoming pregnant (in case of active sexual life adequate contraception is obligatory)
- Presence of progressive cerebral disease, any other progressively degenerative neurological disease or cerebral tumours with signs of progression
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2010-018284-42-NL |
| CCMO | NL41142.042.12 |