Recurrent Febrile ConvulsionNCT04364321
Single Dose of Clonazepam Versus Intermiittent Diazepam for Febrile Seizures Prevention
A study testing Clonazepam 0.5 MG and Diazepam Tablets in people with Recurrent Febrile Convulsion, run by Queen Sirikit National Institute of Child Health at 1 site in Thailand.
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. Read more about this study
- Who is it for?
- Ages 6 to 60 months
- Conditions the study is for
- Recurrent Febrile Convulsion
- What is being tested?
- Clonazepam 0.5 MG and Diazepam Tablets
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 74 participants
- Where
- 1 siteThailand
- Study dates
- 13 May 2020to Jun 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 60 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- age 6-60 months at date of enrollment
- 3 or more episodes of clinically diagnosed febrile seizures
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
Thailand1 site, 1 recruiting
- Recruiting
Queen Sirikit National Institute of Child Health
Ratchathewi, Bangkok, 10400
Jinjutha Nithiuthai, MD, jinjutha.nt@gmail.com
Jinjutha Nitiuthai, MD
About this study
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
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.
Read the 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.
- Conditions
- Recurrent Febrile Convulsion
- Being tested
- Clonazepam 0.5 MG, Diazepam Tablets
- Keywords
- recurrent febrile convulsions, Clonazepam, prophylaxis
- Medical subject headings
- Seizures, Febrile
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Clonazepam 0.5 MGDrug
Also called Rivotril, Povanil
Clonazepam 0.02 mg/kg only one dose
Diazepam TabletsDrug
Diazepam 0.3 mg/kg every 8 hours for 3 doses. (24 hr)
| Study group | Role | What they receive |
|---|---|---|
| Single dose Clonazepam | Experimental | Clonazepam(0.5 mg/tablet) 0.02 mg/kg orally once at the time of fever present. (body temperature more than 38 degree Celsius) Receives: Drug: Clonazepam 0.5 MG |
| Intermittent oral diazepam | Active comparator | 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. Receives: Drug: Diazepam Tablets |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: the assessment will be done at 12 months after enrollment
Secondary outcomes (8)
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.
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: at the enrollment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Apr 2020
- Study start13 May 2020
- Primary completionJun 2023 (estimated)
- Study completionJun 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for Recurrent Febrile ConvulsionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- A pragmatic parallel group randomized trial comparing single dose clonazepam with intermittent oral diazepam for prevention recurrent febrile seizures
- Masking
- Triple blind
- Who is masked
- Care provider, Investigator, Outcomes assessor
- Enrolment
- 74 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Queen Sirikit National Institute of Child Health
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Kullasate Sakpichaisakul, Queen Sirikit National Institute of Child Health
- Investigators
- Jinjutha Nithiuthai, MD, Principal investigator, Queen Sirikit National Institute of Child Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04364321
- Sponsor's protocol ID
- QSNICH63-017
- Status last verified
- Aug 2021
- First submitted
- 5 Apr 2020
- Last updated
- 30 Aug 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: There is no plan to make IPD available due to the confidentiality.
Publications
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. doi: 10.1001/archpedi.1997.02170410045006.
PubMed 9111436Berg AT, Shinnar S, Hauser WA, Leventhal JM. Predictors of recurrent febrile seizures: a metaanalytic review. J Pediatr. 1990 Mar;116(3):329-37. doi: 10.1016/s0022-3476(05)82816-1.
PubMed 2137875Kolfen W, Pehle K, Konig S. Is the long-term outcome of children following febrile convulsions favorable? Dev Med Child Neurol. 1998 Oct;40(10):667-71. doi: 10.1111/j.1469-8749.1998.tb12326.x.
PubMed 9851235Visser 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.
PubMed 22937894Bertelsen EN, Larsen JT, Petersen L, Christensen J, Dalsgaard S. Childhood Epilepsy, Febrile Seizures, and Subsequent Risk of ADHD. Pediatrics. 2016 Aug;138(2):e20154654. doi: 10.1542/peds.2015-4654. Epub 2016 Jul 13.
PubMed 27412639Billstedt 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.
PubMed 31618476Rosman 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. doi: 10.1056/NEJM199307083290202.
PubMed 8510706Knudsen FU. Recurrence risk after first febrile seizure and effect of short term diazepam prophylaxis. Arch Dis Child. 1985 Nov;60(11):1045-9. doi: 10.1136/adc.60.11.1045.
PubMed 3907504Capovilla 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.
PubMed 19125841Offringa M, Newton R, Cozijnsen MA, Nevitt SJ. Prophylactic drug management for febrile seizures in children. Cochrane Database Syst Rev. 2017 Feb 22;2(2):CD003031. doi: 10.1002/14651858.CD003031.pub3.
PubMed 28225210
Study at a glance
From the registry record, last updated by the sponsor on 30 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04364321
- Acronym / sponsor ID
- QSNICH63-017
- Conditions
- Recurrent Febrile Convulsion
- Keywords
- recurrent febrile convulsions, Clonazepam, prophylaxis
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 74 participants (estimated)
- Lead sponsor
- Queen Sirikit National Institute of Child HealthOther government
- Study start
- 13 May 2020 (actual)
- Primary completion
- Jun 2023 (estimated)
- Study completion
- Jun 2023 (estimated)
- First posted
- 28 Apr 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- A pragmatic parallel group randomized trial comparing single dose clonazepam with intermittent oral diazepam for prevention recurrent febrile seizures
| Arm | Type | Receives |
|---|---|---|
| Single dose Clonazepam | Experimental | Drug: Clonazepam 0.5 MGClonazepam(0.5 mg/tablet) 0.02 mg/kg orally once at the time of fever present. (body temperature more than 38 degree Celsius) |
| Intermittent oral diazepam | Active comparator | Drug: Diazepam TabletsDiazepam 0.3 mg/kg every 8 hours for 3 doses. (24 hr) start at the time of body temperature more than 38 degree Celsius. |
Who may qualify
- Ages
- 6 to 60 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (2 listed)
- age 6-60 months at date of enrollment
- 3 or more episodes of clinically diagnosed febrile seizures
Key exclusion criteria (7 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Clonazepam 0.5 MGAlso: Rivotril, PovanilClonazepam 0.02 mg/kg only one dose | Drug | Single dose Clonazepam |
| Diazepam TabletsDiazepam 0.3 mg/kg every 8 hours for 3 doses. (24 hr) | Drug | Intermittent oral diazepam |
Primary outcome
Recurrent rate of febrile seizures
Time frame: 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.
8 secondary outcomes
Number of participants with adverse reaction of medications
Time frame: 7 days
Associated factors: Sex
Time frame: at the enrollment.
Associated factors: age at first febrile seizure
Time frame: at the enrollment
Associated factors: the lowest temperature that cause seizure
Time frame: at the enrollment.
Number of participants with febrile convulsions in parents or siblings
Time frame: at the enrollment.
Number of participants with epilepsy in parents or siblings
Time frame: at the enrollment.
Number of participants with type of febrile seizures (simple or complex)
Time frame: at the enrollment.
Number of participants with delayed developmental milestones
Time frame: at the enrollment.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Aug 2021.
- Background: PubMed 9111436Berg 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. doi: 10.1001/archpedi.1997.02170410045006.
- Background: PubMed 2137875Berg AT, Shinnar S, Hauser WA, Leventhal JM. Predictors of recurrent febrile seizures: a metaanalytic review. J Pediatr. 1990 Mar;116(3):329-37. doi: 10.1016/s0022-3476(05)82816-1.
- Background: PubMed 9851235Kolfen W, Pehle K, Konig S. Is the long-term outcome of children following febrile convulsions favorable? Dev Med Child Neurol. 1998 Oct;40(10):667-71. doi: 10.1111/j.1469-8749.1998.tb12326.x.
- Background: PubMed 22937894Visser 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.
- Background: PubMed 27412639Bertelsen EN, Larsen JT, Petersen L, Christensen J, Dalsgaard S. Childhood Epilepsy, Febrile Seizures, and Subsequent Risk of ADHD. Pediatrics. 2016 Aug;138(2):e20154654. doi: 10.1542/peds.2015-4654. Epub 2016 Jul 13.
- Background: PubMed 31618476Billstedt 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.
- Results publication: PubMed 8510706Rosman 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. doi: 10.1056/NEJM199307083290202.
- Results publication: PubMed 3907504Knudsen FU. Recurrence risk after first febrile seizure and effect of short term diazepam prophylaxis. Arch Dis Child. 1985 Nov;60(11):1045-9. doi: 10.1136/adc.60.11.1045.
- Results publication: PubMed 19125841Capovilla 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.
- Results publication: PubMed 28225210Offringa M, Newton R, Cozijnsen MA, Nevitt SJ. Prophylactic drug management for febrile seizures in children. Cochrane Database Syst Rev. 2017 Feb 22;2(2):CD003031. doi: 10.1002/14651858.CD003031.pub3.
- Individual participant dataSharing planned: No. There is no plan to make IPD available due to the confidentiality.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jinjutha Nithiuthai, MD principal investigator
Queen Sirikit National Institute of Child Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Clonazepam 0.5 MG and Diazepam Tablets in people with Recurrent Febrile Convulsion, run by Queen Sirikit National Institute of Child Health at 1 site in Thailand.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 30 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Thailand. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jinjutha Nithiuthai, MD (66806218033, jinjutha.nt@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Recurrent rate of febrile seizures (time frame: the assessment will be done at 12 months after enrollment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04364321, which also lists 10 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Aug 2021.