Single Dose of Clonazepam Versus Intermiittent Diazepam for Febrile Seizures Prevention

Recurrent Febrile Convulsion Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04364321
• Other study ID #: QSNICH63-017
• Status: Recruiting
• Phase: N/A
• Start date: May 13, 2020
• Est. completion date: June 2023

Study information

• Verified date: August 2021
• Source: Queen Sirikit National Institute of Child Health
• Contact: Jinjutha Nithiuthai, MD
• Phone: 66806218033
• Email: jinjutha.nt[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 74
• Est. completion date: June 2023
• Est. primary completion date: June 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 60 Months

Eligibility

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.

Related Conditions & MeSH terms

• Fever
• Recurrent Febrile Convulsion
• Seizures
• Seizures, Febrile

Intervention

Drug:
• Clonazepam 0.5 MG
Clonazepam 0.02 mg/kg only one dose
• Diazepam Tablets
Diazepam 0.3 mg/kg every 8 hours for 3 doses. (24 hr)

Locations

Country	Name	City	State
Thailand	Queen Sirikit National Institute of Child Health	Ratchathewi	Bangkok

Sponsors (1)

Lead Sponsor	Collaborator
Queen Sirikit National Institute of Child Health

Country where clinical trial is conducted

Thailand, 

References & Publications (10)

Berg AT, Shinnar S, Darefsky AS, Holford TR, Shapiro ED, Salomon ME, Crain EF, Hauser AW. Predictors of recurrent febrile seizures. A prospective cohort study. Arch Pediatr Adolesc Med. 1997 Apr;151(4):371-8. — View Citation

Berg AT, Shinnar S, Hauser WA, Leventhal JM. Predictors of recurrent febrile seizures: a metaanalytic review. J Pediatr. 1990 Mar;116(3):329-37. — View Citation

Bertelsen EN, Larsen JT, Petersen L, Christensen J, Dalsgaard S. Childhood Epilepsy, Febrile Seizures, and Subsequent Risk of ADHD. Pediatrics. 2016 Aug;138(2). pii: e20154654. doi: 10.1542/peds.2015-4654. Epub 2016 Jul 13. — View Citation

Billstedt E, Nilsson G, Leffler L, Carlsson L, Olsson I, Fernell E, Gillberg C. Cognitive functioning in a representative cohort of preschool children with febrile seizures. Acta Paediatr. 2020 May;109(5):989-994. doi: 10.1111/apa.15059. Epub 2019 Nov 10. — View Citation

Capovilla G, Mastrangelo M, Romeo A, Vigevano F. Recommendations for the management of "febrile seizures": Ad Hoc Task Force of LICE Guidelines Commission. Epilepsia. 2009 Jan;50 Suppl 1:2-6. doi: 10.1111/j.1528-1167.2008.01963.x. Review. — View Citation

Knudsen FU. Recurrence risk after first febrile seizure and effect of short term diazepam prophylaxis. Arch Dis Child. 1985 Nov;60(11):1045-9. — View Citation

Kölfen W, Pehle K, König S. Is the long-term outcome of children following febrile convulsions favorable? Dev Med Child Neurol. 1998 Oct;40(10):667-71. — View Citation

Offringa M, Newton R, Cozijnsen MA, Nevitt SJ. Prophylactic drug management for febrile seizures in children. Cochrane Database Syst Rev. 2017 Feb 22;2:CD003031. doi: 10.1002/14651858.CD003031.pub3. Review. Update in: Cochrane Database Syst Rev. 2021 Jun — View Citation

Rosman NP, Colton T, Labazzo J, Gilbert PL, Gardella NB, Kaye EM, Van Bennekom C, Winter MR. A controlled trial of diazepam administered during febrile illnesses to prevent recurrence of febrile seizures. N Engl J Med. 1993 Jul 8;329(2):79-84. — View Citation

Visser AM, Jaddoe VW, Ghassabian A, Schenk JJ, Verhulst FC, Hofman A, Tiemeier H, Moll HA, Arts WF. Febrile seizures and behavioural and cognitive outcomes in preschool children: the Generation R study. Dev Med Child Neurol. 2012 Nov;54(11):1006-11. doi: 10.1111/j.1469-8749.2012.04405.x. Epub 2012 Sep 3. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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.
Secondary	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
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.

External Links

•   Intermittent Clonazepam in the prevention of recurrent febrile seiziures