The Benefit and Safety of Older Generation Anti-Epileptic Drugs (AEDs) in Drug-Resistant Epilepsy Children

Dr Cipto Mangunkusumo General Hospital

Status and phase: Enrolling; Phase 4

Conditions: Drug Resistant Epilepsy

Treatments: Drug: Clobazam; Drug: Oxcarbazepine; Drug: Carbamazepin; Drug: Phenytoin; Drug: Lamotrigine; Drug: Valproic acid

Study type: Interventional

Funder types: Other

Identifiers

NCT05697614

22-09-1097

Details and patient eligibility

About

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.

Full 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.

Enrollment: 100 estimated patients

Sex: All

Ages: 1 to 18 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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100 participants in 2 patient groups

intervention

Experimental group

Description:

valproic acid 15 - 60 mg/kg body weight/day, divided into 2 dosages/day for 12 weeks ; carbamazepine 10 - 30 mg/kg body weight/day, divided into 2 dosages/day for 12 weeks ; phenytoin 5-7 mg/kg body weight/day, divided into 2 dosages/day for 12 weeks

Treatment:

Drug: Valproic acid

Drug: Phenytoin

Drug: Carbamazepin

control

Active Comparator group

Description:

lamotrigine 0.2 mg/kg body weight/day, divided into 2 dosages/day for 12 weeks ; clobazam 0.1 - 0.8 body weight/day, divided into 2 dosages/day for 12 weeks ; oxcarbazepine10 - 30 mg/kg body weight/day, divided into 2 dosages/day for 12 weeks

Treatment:

Drug: Lamotrigine

Drug: Oxcarbazepine

Drug: Clobazam