Clinical trial NCT05697614: The Benefit and Safety of Older Generation Anti-Epileptic Drugs (AEDs) in Drug-Resistant Epilepsy Children
Official title: The Efficacy and Safety of First-Line Anti-Epileptic Drugs (AEDs) as Substitution Therapy in Children Who Are Resistant to Second-Line AEDs
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Drug Resistant Epilepsy
Keywords: anti-epilepsy drug
children
epilepsy
resistant
Lead sponsor: Dr Cipto Mangunkusumo General Hospital
Sponsor class: OTHER
First posted: 2023-01-26
Enrollment: 100
Sex: ALL
Minimum age (years): 1
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The subjects will be randomized into 2 groups : intervention and control. The subjects will be recruited by consecutive sampling technique
Primary purpose: TREATMENT

Brief summary: The goal of this interventional study is to learn about the efficacy and safety of first line anti epileptic drugs (AEDs) as substitution therapy for children who are resistant to second-line AEDs. The main question to answer it aims are :

how much the difference proportion of responders (responders are children who achieve the decrease of seizure frequencies by 50%) how much time it is needed to achieve the decrease of seizure frequencies by 50% The patients who are eligible for the study and have given their consent, will be enrolled, divided into 2 groups, the control and intervention.

The participant should follow the 14 weeks of intervention that consists of 6 phases : baseline, initial dose, titration dose, maintenance dose, tapering-off dose, and new combination maintenance dose.

Detailed description: Each phase of the study is described below

In baseline phase, data such as demographic, clinical characteristic including seizure frequency, seizure type, seizure onset, medication history, family history of seizure, and also developmental stages, will be recorded from electronic medical record. Besides, the CT-scan or MRI are also collected from the same source. After that, their quality of life will be assessed by QOLCE-55 validated questionnaire through self-guided report. Furthermore, the laboratory investigation and EEG will be performed.

The next phase is intervention phase, started from initial phase and ended by the maintenance of new combination therapy phase, takes with overall 12 weeks. Initially, the substitution drugs with each initial dose are consumed. The drugs consist of valproic acid for the generalized and carbamazepine for focal epilepsies.

On the other hand, the control group will take lamotrigine or clobazam for generalized and oxcarbazepine for focal ones. The phase continuous to titration dose, in which, the dose is raised gradually until it causes 50% of seizure reduction, and the next step is maintained the dose for about 2 weeks.

- The following is tapering-off and after that stopping the substituted drug, levetiracetam or topiramate, which is determined by considering individual condition. Yet, if the seizures increase more than one and a half time of the previous frequency during the phases, the intervention will be ended immediately. On the contrary, if the condition is better, then the children go to the maintenance of new combination, that is the substitution drug and the old drugs in which the seizures do not go up or even better keep going down.

Eligibility criteria: Inclusion Criteria:

1. Children age at 1 - 18 years old
2. Children diagnosed as drug-resistant epilepsy by pediatric neurologists, diagnosis was based on the ILAE 2017 criteria
3. Children will have got at least 3 months of combination therapy that consists of levetiracetam of topiramate with optimal dosage but haven't got seizure reduction

Exclusion Criteria:

1. Non-convulsive epilepsy
2. Suffered from status epilepticus in the prior 3 months before the study begins Past medical history of idiosyncrasies or severe adverse drug reactions caused by the
3. substitution therapy that will be given

Primary outcomes:
measure: the different proportion of responders between groups who get first-line anti-epileptic drugs (intervention) and second-line anti-epileptic drugs (control)
timeFrame: trough the study completion, about 14 weeks
Secondary outcomes:
measure: time to achieve the reduction of seizure frequency by 50% or more among responders
timeFrame: during intervention, about 12 weeks
measure: the difference of quality of life between groups who get first-line anti-epileptic drugs (intervention) and second-line anti-epileptic drugs (control)
timeFrame: at baseline phase in the 1st week (before intervention) and after intervention in the 14th week
measure: the difference of the electroencephalography (EEG) changing between groups who get first-line anti-epileptic drugs (intervention) and second-line anti-epileptic drugs (control)
timeFrame: at baseline phase in the 1st week (before intervention) and after intervention in the 14th week
measure: the description of age in percentage
timeFrame: at baseline phase in the 1st week (before intervention)
measure: the description of seizure onset in percentage
timeFrame: at baseline phase in the 1st week (before intervention)
measure: the description of gender in percentage
timeFrame: at baseline phase at 1st week (before intervention)
measure: the description duration of anti epileptic drug medication
timeFrame: at baseline phase at 1st week (before intervention)
measure: The brain CT or brain MRI
timeFrame: at baseline phase at 1st week (before intervention)
measure: The adverse drug reaction profile in percentage
timeFrame: during intervention, about 12 weeks
measure: seizure frequency
timeFrame: during intervention, about 12 weeks
measure: the history of developmental delayed
timeFrame: at baseline phase at 1st week (before intervention)
measure: the number of anti-epileptic drug is consumed
timeFrame: at baseline phase at 1st week (before intervention)
measure: the history of seizure in the family
timeFrame: at baseline phase at 1st week (before intervention)
measure: the association between age and seizure reduction
timeFrame: after intervention in the 14th week
measure: the association between seizure onset and seizure reduction
timeFrame: after intervention in the 14th week
measure: the association between gender and seizure reduction
timeFrame: after intervention in the 14th week
measure: the association between duration of anti epileptic drug medication and seizure reduction
timeFrame: after intervention in the 14th week
measure: the association of the brain CT or brain MRI and seizure reduction
timeFrame: after intervention in the 14th week
measure: the association of seizure frequency and seizure reduction
timeFrame: after intervention in the 14th week
measure: the association between the history of developmental delayed and seizure reduction
timeFrame: after intervention in the 14th week
measure: the association of the number of anti-epileptic drug is consumed and seizure reduction
timeFrame: after intervention in the 14th week
measure: the association between the history of seizure in the family and seizure reduction
timeFrame: after intervention in the 14th week
Other outcomes:
Locations:
city: Jakarta Pusat
country: Indonesia
facility: Cipto Mangunkusumo Hospital
state: Jakarta
city: Jakarta
country: Indonesia
facility: Harapan Kita Hospital
city: Jakarta
country: Indonesia
facility: Fatmawati Hospital
Study officials:
affiliation: Cipto Mangunkusumo Hopsital - Medical Faculty of Indonesia University
name: Roro Rukmi Windi Perdani Pediatrician
role: PRINCIPAL_INVESTIGATOR
References: