Single Dose of Clonazepam Versus Intermiittent Diazepam for Febrile Seizures Prevention

Study Overview
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Brief Summary
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To study the efficacy and safety of single dose clonazepam compared with intermittent oral diazepam for prevention of recurrent febrile seizures in children who had three or more febrile seizures.

Detailed Description
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Febrile seizures are the most common type of seizures disorder of young children. The risk of recurrences are 33 percent overall, half of them had at least one recurrent seizure (the 3rd febrile seizures). After that the recurrent rate is 50-100 percent depend on their risk factors. A few studies found that multiple recurrent febrile seizures might associated with language developmental delayed, poor speed performance quotient, Attention deficit hyperactivity disorders. Moreover, seizures are upsetting both parents and children. During the febrile illness, the intermittent diazepam, continuous phenobarbital and valproate are effective for prevention of the recurrences. Because of the benign nature of a simple febrile seizures, the risks of side effects generally outweigh the benefits. However, there is no clinical guidelines for prevention of recurrent febrile seizures in the children who experienced multiple occurrences. The better prophylactic drug; safe, effective and easy to use, for prevention of recurrent febrile seizures in children with multiple recurrences might be needed. Clonazepam, the long half-life benzodiazepine, is commonly used for treatment of epilepsy may be effective in preventing recurrent febrile seizures. This study, a single-blind, randomized clinical trial, single dose clonazepam at the time of fever present compared with oral diazepam during the fever to prevent the recurrent febrile seizures.

Official Title
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The Efficacy of A Single Dose Clonazepam Compared With the Intermittent Diazepam to Prevent Recurrent Febrile Seizures in Queen Sirikit National Institute of Child Health

Conditions
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Recurrent Febrile Convulsion

Intervention / Treatment
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* Drug: Clonazepam 0.5 MG
* Drug: Diazepam Tablets


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age 6-60 months at date of enrollment 3 or more episodes of clinically diagnosed febrile seizures Exclusion Criteria: history of afebrile seizures or any history suggested the epilepsy history of previous brain insults; CNS infection, birth trauma, traumatic brain injury. delayed developmental milestones abnormal neurological examinations currently treatment by continous antiepileptic drug(s) A contraindication to Clonazepam, Diazepam such as drug hypersensitivity, liver disease. Predictable lack of available of follow up.

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 60 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A pragmatic parallel group randomized trial comparing single dose clonazepam with intermittent oral diazepam for prevention recurrent febrile seizures
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single dose Clonazepam<br>Clonazepam(0.5 mg/tablet) 0.02 mg/kg orally once at the time of fever present. (body temperature more than 38 degree Celsius) | Drug: Clonazepam 0.5 MG<br>* Clonazepam 0.02 mg/kg only one dose<br>* Other names: Povanil;|
| Active Comparator: Intermittent oral diazepam<br>Diazepam 0.3 mg/kg every 8 hours for 3 doses. (24 hr) start at the time of body temperature more than 38 degree Celsius. | Drug: Diazepam Tablets<br>* Diazepam 0.3 mg/kg every 8 hours for 3 doses. (24 hr)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrent rate of febrile seizures | Rate of seizure occurs when the children have febrile illnesses (at the onset of fever until fever gone). The seizures will be reported by their parents/caregivers. (via the seizure record form and the interview.) Statistic analysis: Cumulative incidence (person-year). percent. Comparison between the two group by unpaired t test. | the assessment will be done at 12 months after enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse reaction of medications | The adverse reactions will be recorded by their caregivers in the record form for 7 days since patients taking the medication (clonapam or diazepam). The adverse reactions are drowsiness, ataxia, irritability, drooling, insomnia and rashes. Statistic analysis: cumulative incidence (person-year), Comparison between the two group by unpaired t test. | 7 days | 
| Associated factors: Sex | To evaluate the associated factors of multiple recurrent febrile seizures. The data will be collected in the record form by the primary investigator at the enrollment. Statistic analysis: comparison between group by chi square | at the enrollment. | 
| Associated factors: age at first febrile seizure | To evaluate the associated factors of multiple recurrent febrile seizures. The data will be collected in the record form by interviewing the caregivers to recall the information. Statistic analysis: comparison between group by unpaired t test | at the enrollment | 
| Associated factors: the lowest temperature that cause seizure | To evaluate the associated factors of multiple recurrent febrile seizures. The data will be collected in the record form by interviewing the caregivers to recall the information. Statistic analysis: comparison between group by unpaired t test | at the enrollment. | 
| Number of participants with febrile convulsions in parents or siblings | To evaluate the associated factors of multiple recurrent febrile seizures. The data will be collected in the record form by interviewing the caregivers. Statistic analysis: comparison between group by chi square | at the enrollment. | 
| Number of participants with epilepsy in parents or siblings | To evaluate the associated factors of multiple recurrent febrile seizures. The data will be collected in the record form by interviewing the caregivers. Statistic analysis: comparison between group by chi square | at the enrollment. | 
| Number of participants with type of febrile seizures (simple or complex) | To evaluate the associated factors of multiple recurrent febrile seizures. Type of febrile seizure simple: seizure duration less than 15 min, generalized seizures, one seizure in 24 hours complex:15 minutes or more and/or focal seizures and/or 2 or more seizures in 24 hours The data will be collected in the record form by interviewing the caregivers. Statistic analysis: comparison between group by chi square | at the enrollment. | 
| Number of participants with delayed developmental milestones | The data will be collected by the developmental screening tools; Age and Stages Questionaires, third edition reported by the caregivers. Scoring will be done by neurology pediatrician at the enrollment. Age and Stages Questionaires(third editon) are divided in 5 areas; communication, gross motor, fine motor, problem solving, personal-social, each area has 6 questions. Scores for each area are between 0 to 60. The Cutoff points are different in each area. If the score is above the cutoff, the children development appears normal for age. (The cutoff for communication is 29.65, Gross motor is 22.25, fine motor is 25.14, problem solving is 27.72 and personal-social is 25.34) Statistic analysis: comparison between group by unpaired t test | at the enrollment. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent febrile convulsions, Clonazepam, prophylaxis