The Efficacy and Safety of First-Line Anti-Epileptic Drugs (AEDs) as Substitution Therapy in Children Who Are Resistant to Second-Line AEDs
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 100
- 试验地点
- 3
- 主要终点
- the different proportion of responders between groups who get first-line anti-epileptic drugs (intervention) and second-line anti-epileptic drugs (control)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 1 Year 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Children age at 1 - 18 years old
- •Children diagnosed as drug-resistant epilepsy by pediatric neurologists, diagnosis was based on the ILAE 2017 criteria
- •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
排除标准
- •Non-convulsive epilepsy
- •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
- •substitution therapy that will be given
研究组 & 干预措施
intervention
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
干预措施: Valproic acid (Drug)
intervention
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
干预措施: Carbamazepin (Drug)
intervention
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
干预措施: Phenytoin (Drug)
control
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
干预措施: Lamotrigine (Drug)
control
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
干预措施: Clobazam (Drug)
control
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
干预措施: Oxcarbazepine (Drug)
结局指标
主要结局
the different proportion of responders between groups who get first-line anti-epileptic drugs (intervention) and second-line anti-epileptic drugs (control)
时间窗: trough the study completion, about 14 weeks
responders are children who get the reduction of seizure frequency by 50%
次要结局
- the description of seizure onset in percentage(at baseline phase in the 1st week (before intervention))
- time to achieve the reduction of seizure frequency by 50% or more among responders(during intervention, about 12 weeks)
- the difference of quality of life between groups who get first-line anti-epileptic drugs (intervention) and second-line anti-epileptic drugs (control)(at baseline phase in the 1st week (before intervention) and after intervention in the 14th week)
- the difference of the electroencephalography (EEG) changing between groups who get first-line anti-epileptic drugs (intervention) and second-line anti-epileptic drugs (control)(at baseline phase in the 1st week (before intervention) and after intervention in the 14th week)
- the description of age in percentage(at baseline phase in the 1st week (before intervention))
- the description of gender in percentage(at baseline phase at 1st week (before intervention))
- the history of seizure in the family(at baseline phase at 1st week (before intervention))
- the association between age and seizure reduction(after intervention in the 14th week)
- the association of the brain CT or brain MRI and seizure reduction(after intervention in the 14th week)
- the description duration of anti epileptic drug medication(at baseline phase at 1st week (before intervention))
- seizure frequency(during intervention, about 12 weeks)
- the number of anti-epileptic drug is consumed(at baseline phase at 1st week (before intervention))
- the association between seizure onset and seizure reduction(after intervention in the 14th week)
- The brain CT or brain MRI(at baseline phase at 1st week (before intervention))
- The adverse drug reaction profile in percentage(during intervention, about 12 weeks)
- the association between gender and seizure reduction(after intervention in the 14th week)
- the association between duration of anti epileptic drug medication and seizure reduction(after intervention in the 14th week)
- the association of the number of anti-epileptic drug is consumed and seizure reduction(after intervention in the 14th week)
- the history of developmental delayed(at baseline phase at 1st week (before intervention))
- the association of seizure frequency and seizure reduction(after intervention in the 14th week)
- the association between the history of developmental delayed and seizure reduction(after intervention in the 14th week)
- the association between the history of seizure in the family and seizure reduction(after intervention in the 14th week)
研究者
Roro Rukmi Windi Perdani
Principal investigator
Dr Cipto Mangunkusumo General Hospital