Intractable epilepsy Nervous System Diseases Other epilepsy
Conditions
Interventions
The Time to Stop trial will compare an early AED withdrawal group, that starts reduction of AEDs four months after surgery and completes withdrawal within eight months after start of withdrawal, with
Sponsors
University Medical Center Utrecht (Netherlands)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Younger than 16 years at surgery, with focal non-idiopathic epilepsy 2. Native speaker in the language the neuropsychological tests have to be taken 3. Be able to perform a Conner's Performance Test preoperatively (generally that means age > 4 yrs, and IQ > 60) 4. Underwent intentional curative epilepsy surgery 5. After surgery, the treating physician considers withdrawal of antiepileptic drugs (AEDs), with the intention to completely discontinue medication, at whatever point in time. 6. Both the treating physician, the patient, if capable, and the parents agree with randomization in either arm of the study 7. Postoperative seizure freedom was achieved (with the exception of so called running down seizures not outlasting longer than two weeks)
Exclusion criteria
Exclusion criteria: 1. A contraindication to be randomized to either of the two withdrawal arms 2. The treating physician does not want to discontinue all AEDs within a maximum time frame of eight months as prescribed in the study protocol. 3. Multifocal MRI abnormalities, incomplete resection of the anatomical or epileptogenic lesion certified before randomisation (if considered necessary by the treating physician by MRI) and, if a postoperative EEG is performed before randomisation, epileptic EEG abnormalities (these being the most important risk factors of seizure recurrence or unfavourable long-term seizure outcome). 4. Use of more than three AEDs at time of surgery. The reason to choose for a maximum of three AEDs is that clinicians would not want to wait 12 months (the late withdrawal arm) to withdraw the first AED in patients that use so many AEDs. Furthermore, withdrawing AEDs within 8 months seems reasonable and feasible for a maximum of three AEDs. 5. Patients who are on a ketogenic diet or have a vagal nerve stimulator implanted. 6. If surgery is primarily intended as tumor surgery and not as epilepsy surgery
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary objective of the study is to assess whether early AED withdrawal improves cognitive function, in terms of attention, information processing- and psychomotor speed, memory, language and IQ/DQ scores. Attention will be the main outcome measure, on which the power calculation is based. Attention deficits (AD) are assessed using a Conner's Performance (Kiddie) test and calculate IQ/DQ scores. The other neuropsychological domains will be assessed by subtests of the intelligence tests. We will compare neuropsychological outcome between the two withdrawal groups at t1 (preoperatively), t2 (at 12 months) and t3 (at 24 months). | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. To confirm safety, in terms of seizure recurrences, long term seizure freedom and cure, of early AED withdrawal. In the randomized trial we determine long-term seizure outcome and cure at 20 months following intended start of AED reduction (being theoretically 'at risk' during an identical time window in both groups). Seizure freedom will be defined as complete seizure freedom for at least one year [Engel 1(3) of International League Against Epilepsy (ILAE) 1-2(4)], and cure as seizure freedom and AED freedom for at least one year. The existence of seizure recurrences will be measured every time the patient visits her/his epileptologist, and if parents call the hospital to report seizure recurrences. 2. To compare behavioural problems between the two withdrawal groups, parents of participants will, at both postoperative neuropsychological test points, complete a Child Behavior Checklist (CBCL) (12 and 24 months postoperatively) 3. To compare quality of life between the two withdrawal groups. Patients will, at both postoperative neuropsychological test points, complete a Pediatric Quality of Life InventoryTM (PedsQL™) and the The Hague Side Effects Scale (HASES) (12 and 24 months postoperatively). | — |
Countries
France, Germany, Netherlands, Switzerland, United Kingdom
Outcome results
None listed