Primary Objective: To assess whether early postoperative AED withdrawal improves cognitive function compared to late withdrawal.Secondary objectives: * To confirm safety of earlier AED withdrawal; we will assess eventual seizure freedom, seizure…
ID
Source
Brief title
Condition
- Seizures (incl subtypes)
- Nervous system, skull and spine therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary outcome: change in neurocognitive domains (expressed as EpiTrack scores
and IQ) at one and two years after surgery, compared with presurgical
functioning. (research protocol page 22, paragraph 7.1.1.)
Secondary outcome
seizure recurrences, eventual seizure freedom and *cure* at 20 months following
start of AED reduction, quality of life and behaviour.
Background summary
*Cure*, is the ultimate goal for epilepsy surgery. We recently showed that
early AED withdrawal seemed safe in a selected subgroup of successfully
operated patients, without the identified unfavourable predictors for seizure
recurrences during or after AED withdrawal or eventual seizure freedom
(epileptic EEG abnormalities, multifocal MRI lesions and incomplete resection
of the lesion). We question if early AED withdrawal is also beneficial for
children with regard to cognition. Our hypothesis is that early withdrawal is
beneficial for patients with respect to their cognition.
Study objective
Primary Objective: To assess whether early postoperative AED withdrawal
improves cognitive function compared to late withdrawal.
Secondary objectives:
* To confirm safety of earlier AED withdrawal; we will assess eventual seizure
freedom, seizure recurrences and *cure* as outcome measure at latest follow up.
(Engel 1 or ILAE 1-2 for at least 1 year).
* To assess whether early AED withdrawal improves quality of life after
epilepsy surgery.
* To compare behavioural problems between the two withdrawal groups
Study design
randomized trial with blinded primary outcome measure, in which an early AED
withdrawal group in which postoperatively seizure free patients will start
tapering off AEDs 4 months after surgery, will be compared to a late AED
withdrawal group in which seizure free patients will start tapering off AEDs 12
months after surgery.
Intervention
The intervention group will start tapering off medication 4 months
postoperatively instead of the conventional 12 months postoperatively. The
taper period may take maximally 8 months in both groups.
Study burden and risks
Early AED withdrawal has been proven safe in our recently completed European
retrospective cohort study. The by us identified predictors of unfavorable
outcome, have been defined as exclusion criteria for participation in the
current proposed trial, in order to ensure safety (multifocal MRI
abnormalities, incomplete resection of the anatomical lesion or epileptogenic
lesion, epileptic abnormalities on postoperative EEC [if performed], and more
than three AEDs preoperatively).
As in the protocol, and at point E9 described, we have performed a test
analysis on our retrospective database, with children who would qualify for the
current trial. In this group we found no relationship between the interval to
AED reduction and the occurrence of relapses during or after AED withdrawal. We
expect a similar rate of recurrence in both treatment arms, corresponding to
the number of relapses in daily clinical practice. The DSMB will monitor
safety, blinded by the number of recurrences in both arms control.
With regard to extent of the burden: the number of hospital visits will be the
same as in normal clinical care. The regular neuropsychological examination for
children undergoing epilepsy surgery contains IQ testing and the EpiTrack
Junior. Additionally for the purpose of this trial, patients will be asked to
fulfill quality of life questionnaires 12 - and 24 months after surgery (at the
time of neuropsychological assessment), which will take up to 5-10 minutes, for
the smaller children or infants who are mentally incapable, the questionnaire
will be done by parents.
This study van only be performed in the proposed population as it is group
related: medication can be withdrawn sooner and safer in children than in
adults as described previously and cognitive side effects have more
consequences in children as their brain is still in the process of maturation.
Plus, in adults, the possibly increased relapse rate associated with early AED
discontinuation has a much higher impact than in children, as it may lead to a
temporary license suspension, stigmatization and obstruction of professional
careers. For children, however, the possible slightly increased risk of
recurrences and their impact does, not weigh against the well known
neurocognitive side effects.
Lundlaan 6
Utrecht 3508 AB
NL
Lundlaan 6
Utrecht 3508 AB
NL
Listed location countries
Age
Inclusion criteria
* Younger than 16 years at surgery, with focal non-idiopathic epilepsy, with written informed consent of parents and children when older than 12 years old.
* Native speaker in the language the neuropsychological tests have to be taken
* Be able to perform the EpiTrack Junior preoperatively
* Underwent intentional curative epilepsy surgery
* After surgery, the treating physician considers withdrawal of AEDs, with the intention to completely discontinue medication, at whatever point in time.
* Both the treating physician, the patient, if capable, and the parents agree with randomization in either arm of the study
* Postoperative seizure freedom was achieved (with the exception of so called running down seizures not outlasting longer than two weeks)
Exclusion criteria
* A contraindication to be randomized to either of the two withdrawal arms
* The treating physician does not want to discontinue all AEDs within a maximum time frame of eight months as prescribed in the study protocol.
* 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).
* Use of more than 3 AEDs at time of surgery. The reason to choose for a maximum of 3 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 3 AEDs.
* Patients who are on a ketogenic diet or have a vagal nerve stimulator implanted.
* If surgery is primarily intended as tumor surgery and not as epilepsy surgery
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 | EUCTR2011-005971-18-NL |
| ISRCTN | ISRCTN88423240 |
| CCMO | NL31045.041.13 |