Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623000638639
Ethics application status
Approved
Date submitted
5/05/2023
Date registered
13/06/2023
Date last updated
16/06/2024
Date data sharing statement initially provided
13/06/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
FEBCON-ED Study: Does advice to give regular antipyretics for children presenting with a FEBrile CONvulsion to the Emergency Department reduce the rate of seizure reoccurrence within the same febrile illness?
Scientific title
FEBCON-ED: A stepped- wedge cluster randomised controlled clinical trial of usual care vs regular antipyretics for children presenting with a FEBrile CONvulsion to the Emergency Department.
Secondary ID [1] 309259 0
GNT2015060
Universal Trial Number (UTN)
nil
Trial acronym
FEBCON-ED
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Febrile Convulsions 329417 0
Condition category
Condition code
Emergency medicine 326361 326361 0 0
Other emergency care
Neurological 326362 326362 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Discharge advice recommending the participant take an antipyretic regularly: either paracetamol 15 mg/kg every 6 hours (four times per day) or ibuprofen 10 mg/kg every 8 hours (three times per day) for the first 24 hours after the febrile convulsion. Antipyretic of the parent/guardian's choice will be provided at discharge if participant requires it.

The treating Emergency Department (ED) Clinician will provide the interventional discharge advice face-to-face prior to the participant being discharged home from the ED. Interventional discharge advice will be provided in multiple languages, in hardcopy or electronic formats depending on participant preference. Provision of both verbal and written discharge advice will take less than 5 minutes for the clinician to deliver. Both Participant and Clinician adherence to the intervention will be assessed via the Parent/Guardian questionnaire on day 3 after discharge from the ED. Questions 1,2 and 3 ask the parent/guardian what advice was given, what they understood it to mean, and whether they followed the discharge advice.

Participants will be invited to complete parent/guardian surveys on enrolment, day 3,7 and 12 months post ED discharge for febrile convulsion. These may be completed either via digital platform using a purpose-built study mobile or web app (designed and hosted by Australian digital health software provider WeGuide), or via phone with a member of the study team. Each questionnaire at each data collection time point will comprise of 3-6 questions and take between 2-5 minutes to complete on each occasion.

The FEBCON-ED study utilises a Stepped-Wedge Randomised Clinical Trial (SW-RCT) design and will be undertaken across 25 hospitals within Australia and New Zealand which are members of the PREDICT network. Five hospitals will be randomised to each sequence. There will be six periods, each 6 months in length to account for the seasonal pattern of febrile convulsions enabling an approximately even “split” of the winter peak in cases between each step. Sequential crossover of clusters from control to intervention will occur until all clusters are exposed. Participating hospital ED study sites are randomised at a site level, and interventional discharge advice will be provided to every eligible participant who attends the ED and is discharged home, according to the study site's randomisation sequence.
Intervention code [1] 325696 0
Prevention
Intervention code [2] 325697 0
Treatment: Other
Comparator / control treatment
Standard care discharge advice will be provided to participants in either verbal or written form depending on the Hospitals usual practice ( and in accordance with the study sites prevailing clinical treatment guidelines for febrile convulsions). Current clinical guidelines in Australia and New Zealand recommend “as needed” antipyretics (to treat pain, fever or discomfort) rather than regular administration of antipyretics.
Control group
Active

Outcomes
Primary outcome [1] 334216 0
Reoccurrence of febrile convulsion within the same febrile illness - assessed by parent/guardian report (via outcome survey) and verified by medical record review (composite primary outcome).
Timepoint [1] 334216 0
- 3 and 7 days after ED presentation with febrile convulsion - parent/guardian survey
- 7 days after ED presentation with febrile convulsion - medical record review
Secondary outcome [1] 419865 0
Number of participants who re-present to hospital within 7 days of initial febrile convulsion - assessed by parent/guardian outcome survey and medical record review.
Timepoint [1] 419865 0
At 7 days after ED presentation with febrile convulsion.
Secondary outcome [2] 419870 0
Total number of doses of both antipyretics (paracetamol and/or ibuprofen) given within the first 24hrs after leaving the hospital - assessed by parent/guardian survey (composite secondary outcome).
Timepoint [2] 419870 0
24 hrs after discharge from hospital ED.
Secondary outcome [3] 419872 0
Parental recollection of advice provided by the hospital regarding the use of antipyretics at home - assessed by parent/guardian survey.
Timepoint [3] 419872 0
Days 3 & 7 following discharge from the hospital ED.
Secondary outcome [4] 419873 0
Hospital, GP or other health service use due to febrile convulsions - assessed by parent/guardian reported use via survey, medical record review and data linkage (composite secondary outcome).
Timepoint [4] 419873 0
Days 3, 7 and 12 months post ED discharge for first febrile convulsion.
Secondary outcome [5] 419874 0
App usage data; how often the mobile study app is used by parents during the study period - assessed by the number of parent/guardian surveys completed and within-app data collection.
Timepoint [5] 419874 0
12 months after discharge from ED following the first febrile convulsion.
Secondary outcome [6] 419875 0
Cost of hospitalisation or healthcare services - determined by parent-reported health service use collected in the app. Costs of hospitalisation will be assigned based upon the most up-to-date National Hospital Cost Data Collection, other health services will be costed from the Medicare Benefits Schedule, and prescription pharmaceuticals from the Pharmaceutical Benefits Scheme and equivalent schemes in New Zealand.
Timepoint [6] 419875 0
12 months after discharge from ED following the first febrile convulsion.
Secondary outcome [7] 420611 0
Any incidence of EEG testing - assessed by parent/guardian report via survey, medical record review and data linkage (Medicare Benefits Schedule (AU) National Health Index number (NZ).
Timepoint [7] 420611 0
At 12 months after discharge from ED following the first febrile convulsion.
Secondary outcome [8] 420613 0
Number of participants who re-present to hospital with a febrile convulsion within 12 months of the initial febrile convulsion - assessed by parent/guardian outcome survey, medical record review and data linkage (via Medicare Benefits Scheme, relevant state data linkage units (AU), and National Health Index (NZ))
Timepoint [8] 420613 0
At 12 months after discharge from ED following the first febrile convulsion.
Secondary outcome [9] 420614 0
Prescription of anticonvulsants - assessed by parent/guardian report via survey, medical record review and data linkage (via Pharmaceutical Benefits Scheme and equivalent scheme in New Zealand).
Timepoint [9] 420614 0
At 12 months after discharge from ED following the first febrile convulsion.
Secondary outcome [10] 420615 0
Diagnosis of epilepsy - determined by parent/guardian report via survey, medical record review and data linkage (via Medicare Benefits Scheme, relevant state data linkage units (AU), and National Health Index (NZ)).
Timepoint [10] 420615 0
At 12 months after discharge from ED following the first febrile convulsion.
Secondary outcome [11] 420616 0
Diagnosis of another medical condition - determined by parent/guardian report via survey, medical record review, and data linkage (via Medicare Benefits Scheme, relevant state data linkage units (AU), and National Health Index (NZ)).
Timepoint [11] 420616 0
At 12 months after discharge from ED following the first febrile convulsion.

Eligibility
Key inclusion criteria
A child with an ED diagnosis of a febrile convulsion (defined as a seizure occurring in a child without previous afebrile seizures, without significant prior neurological abnormality and without signs of central nervous system infection or metabolic disturbance) who is planned for discharge home after a period of observation from the ED or ED short stay unit.
Minimum age
6 Months
Maximum age
6 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
(a) a child diagnosed with a febrile convulsion who is planned to be admitted to a hospital ward;
(b) a child with an ED length of stay of greater than 18 hours (to allow for shorter periods of and/or overnight observation in a short-stay unit or similar setting);
(c) a child presenting to the ED with an afebrile convulsion;
(d) a child with a history of epilepsy or a history of afebrile seizures;
(e) a child with status epilepticus requiring at least one second-line agent (such as phenytoin or levetiracetam) to terminate their seizures;
(f) a child with a known allergy to both paracetamol or ibuprofen, or a medical condition in which both these medications would be contraindicated.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
This study is a Stepped-Wedge Randomised Clinical Trial (SW-RCT) across 25 hospitals within paediatric Emergency Departments (EDs) in Australia and New Zealand. Five hospitals will be randomised to each of the 5 clusters. There will be six periods, each 6 months in length to account for the seasonal pattern of febrile convulsions enabling an approximately even “split” of the winter peak in cases between each step. Sequential crossover of clusters from control to intervention will occur until all clusters are exposed.
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
ED and patient demographics will be described by ED and period. All available primary and secondary outcomes will be analysed at the patient level using mixed-effects logistic regression models with a random intercept for cluster-period (allowing for a decay in correlations over time) and fixed effects for each period and for the intervention. The Kenward-Roger correction will be applied to adjust for the small number of EDs. Estimated effects will be expressed as odds ratios and as risk differences, with 95% confidence intervals. Additional subgroup analyses for ethnicity and whether a patient presents with a first or subsequent febrile convulsion will be conducted. Any temporal changes in “usual care” towards the intervention will be assessed using appropriate models. Models for the primary outcome as described above will include terms for the subgroup, and an interaction between subgroup and treatment. Analyses will be conducted in Stata and/or SAS as appropriate.

To determine our sample size, we have assumed that each cluster (participating hospital ED) will have an average of 80 eligible patients within a 6-month period, with a standard deviation of approximately 50 patients, and a coefficient of variation of cluster size of 0.625. Allowing for 20% loss to follow-up, we estimate that data will be available for 64 patients in each cluster in each period. The rate of recurrence of febrile convulsions within the same febrile illness is assumed to be 15%, based on published recurrence rates of between 10.8% and 23.5%. We are aiming to detect a reduction in recurrence of febrile convulsions within the same illness from 15% to 10%.

There is little information available regarding intracluster correlation and within-cluster correlation structures for this outcome. Therefore, we have assumed a conservative range of values for each, to allow for a reasonable power across a range of these parameters. We have allowed for the intracluster correlation (ICC) to range from 0.01 to 0.1 and the decay in the ICC to range from 1 to 0.8 per period. Based on the above assumptions, for this range of correlation parameters, a total of 25 clusters (5 clusters per sequence and a total of 5 sequences) would provide 80% power to demonstrate a change in the rate of recurrent febrile convulsions within the same illness from 15% to 10%. With approximately 64 patients per cluster per period, this equates to 9600 patients over 3 years across 25 participating hospitals.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/02/2024
Actual
22/04/2024
Date of last participant enrolment
Anticipated
31/01/2027
Actual
Date of last data collection
Anticipated
31/01/2028
Actual
Sample size
Target
9600
Accrual to date
72
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,SA,TAS,WA,VIC
Recruitment outside Australia
Country [1] 25341 0
New Zealand
State/province [1] 25341 0

Funding & Sponsors
Funding source category [1] 313453 0
Government body
Name [1] 313453 0
NHMRC
Country [1] 313453 0
Australia
Primary sponsor type
Individual
Name
Prof Simon Craig
Address
Monash University Department of Paediatrics
Level 5, Monash Childrens Hospital
246 Clayton Rd,
Clayton VIC 3168
Country
Australia
Secondary sponsor category [1] 315225 0
Hospital
Name [1] 315225 0
Monash Health
Address [1] 315225 0
246 Clayton Rd,
Clayton VIC 3168
Country [1] 315225 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 312654 0
Monash Health
Ethics committee address [1] 312654 0
Ethics committee country [1] 312654 0
Australia
Date submitted for ethics approval [1] 312654 0
Approval date [1] 312654 0
24/02/2023
Ethics approval number [1] 312654 0
HREC/91710/MonH-2023-350629(v2)

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 125438 0
Prof Simon Craig
Address 125438 0
Monash University Department of Paediatrics,
Level 5, Monash Children's Hospital
246 Clayton Rd
Clayton VIC 3168
Country 125438 0
Australia
Phone 125438 0
+61 03 9594 2707
Fax 125438 0
Email 125438 0
[email protected]
Contact person for public queries
Name 125439 0
Naomi Loftus
Address 125439 0
Monash University Department of Paediatrics,
Level 5, Monash Children's Hospital
246 Clayton Rd
Clayton VIC 3168
Country 125439 0
Australia
Phone 125439 0
+61 3 8572 3961
Fax 125439 0
Email 125439 0
[email protected]
Contact person for scientific queries
Name 125440 0
Simon Craig
Address 125440 0
Monash University Department of Paediatrics,
Level 5, Monash Children's Hospital
246 Clayton Rd
Clayton VIC 3168
Country 125440 0
Australia
Phone 125440 0
+61 03 9594 2707
Fax 125440 0
Email 125440 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Data dictionary.

De-identified individual patient data will be available on reasonable request after approval of the study steering committee.
When will data be available (start and end dates)?
Start date:12 months after publication of results.
End date: 5 years after publication
Available to whom?
Individual researchers and/or collaborative research groups with ethical approval.
Available for what types of analyses?
Individual patient meta-analysis.
How or where can data be obtained?
The study team will review the request and consider the scientific merit of the proposed use of the data, and the legal, regulatory and ethical issues pertinent to the request. Presuming all constraints are addressed, the data will be shared using a secure file transfer platform.

For all data sharing enquiries, please contact Prof Simon Craig via email - [email protected]


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.