Single Dose of Clonazepam Versus Intermiittent Diazepam for Febrile Seizures Prevention

Sponsor

Queen Sirikit National Institute of Child Health (Other)

Overall Status

Recruiting

CT.gov ID

NCT04364321

Collaborator

(none)

Enrollment

Location

Arms

36.6

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Recurrent Febrile Convulsion	Drug: Clonazepam 0.5 MG Drug: Diazepam Tablets	N/A

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

74 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

A pragmatic parallel group randomized trial comparing single dose clonazepam with intermittent oral diazepam for prevention recurrent febrile seizuresA pragmatic parallel group randomized trial comparing single dose clonazepam with intermittent oral diazepam for prevention recurrent febrile seizures

Masking:

Triple (Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

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

Actual Study Start Date :

May 13, 2020

Anticipated Primary Completion Date :

Jun 1, 2023

Anticipated Study Completion Date :

Jun 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Single dose Clonazepam 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 Clonazepam 0.02 mg/kg only one dose Other Names: Rivotril Povanil
Active Comparator: Intermittent oral diazepam 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 Diazepam 0.3 mg/kg every 8 hours for 3 doses. (24 hr)

Arm

Intervention/Treatment

Experimental: Single dose Clonazepam

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

Clonazepam 0.02 mg/kg only one dose

Other Names:

Rivotril

Povanil

Active Comparator: Intermittent oral diazepam

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

Diazepam 0.3 mg/kg every 8 hours for 3 doses. (24 hr)

Outcome Measures

Primary Outcome Measures

Recurrent rate of febrile seizures [the assessment will be done at 12 months after enrollment]
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.

Secondary Outcome Measures

Number of participants with adverse reaction of medications [7 days]
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.
Associated factors: Sex [at the enrollment.]
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
Associated factors: age at first febrile seizure [at the enrollment]
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
Associated factors: the lowest temperature that cause seizure [at the enrollment.]
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
Number of participants with febrile convulsions in parents or siblings [at the enrollment.]
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
Number of participants with epilepsy in parents or siblings [at the enrollment.]
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
Number of participants with type of febrile seizures (simple or complex) [at the enrollment.]
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
Number of participants with delayed developmental milestones [at the enrollment.]
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

6 Months to 60 Months

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.