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Trial registered on ANZCTR


Registration number
ACTRN12615000563561
Ethics application status
Approved
Date submitted
7/05/2015
Date registered
1/06/2015
Date last updated
24/08/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Bell's Palsy in Children: A Multi-centre, double-blind, Randomised, Placebo-controlled Trial to Determine Whether Prednisolone Improves Recovery at 1 Month.
Scientific title
A multi-centre randomised controlled trial of children aged between 6 months and 18 years presenting to emergency departments with symptoms of Bell's palsy, to determine whether treatment with oral prednisolone versus a placebo, increases the proportion of children who have complete recovery at 1 month, where complete recovery is defined as grade 1 on the House Brackmann scale.
Secondary ID [1] 286659 0
Nil
Universal Trial Number (UTN)
U1111-1169-9918
Trial acronym
BellPIC
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Bell's Palsy 294991 0
Condition category
Condition code
Neurological 295256 295256 0 0
Other neurological disorders
Inflammatory and Immune System 295330 295330 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Intervention: Prednisolone.
Prednisolone is a corticosteroid that has strong evidence for effectiveness in reducing the length of facial palsy symptoms in adults suffering from Bell's palsy.
Participants assigned to the intervention will receive 1mg/kg/day of prednisolone (dosing is based on weight categories) up to a maximum of 50mg/day for 10 days.
The prednisolone will be administered as an oral solution as a once daily dose.
Strategies used to monitor adherence will be a survey relating to compliance at the end of the 10 day course of treatment, in addition to the return of the bottles.
Intervention code [1] 291803 0
Treatment: Drugs
Comparator / control treatment
control treatment: placebo.
The placebo will be supplied in glass bottles identical to the intervention by the same supplier that produces the intervention. It will be manufactured to look and taste identical to that of the intervention
The placebo will be an oral liquid with the same ingredients as the intervention solution minus the active drug, prednisolone.
Control group
Placebo

Outcomes
Primary outcome [1] 295004 0
The primary outcome is complete recovery at one month post randomisation, where recovery is defined as a House Brackmann facial grading score of 1. Recovery will be assesed by a specialist clinician in a face to face setting
Timepoint [1] 295004 0
One month post randomisation
Secondary outcome [1] 314557 0
Complete recovery at 1 month using the Sunnybrook facial grading scale assessed by a specialist physician
Timepoint [1] 314557 0
One month post randomisation
Secondary outcome [2] 314558 0
Complete recovery at 3 months using the Sunnybrook facial grading scale assessed by a research assistant
Timepoint [2] 314558 0
Three months post randomisation
Secondary outcome [3] 314559 0
Complete recovery at 3 months using the House Brackmann facial grading scale assessed by a research assistant
Timepoint [3] 314559 0
Three months post randomisation
Secondary outcome [4] 314560 0
Complete recovery at 6 months using the Sunnybrook facial grading scale assessed by a research assistant
Timepoint [4] 314560 0
Six months post randomisation
Secondary outcome [5] 314561 0
Complete recovery at 6 months using the House Brackmann facial grading scale assessed by a research assistant
Timepoint [5] 314561 0
6 months post randomisation
Secondary outcome [6] 314562 0
Parent/guardian and participant (where aged >8 years) perception of facial nerve recovery at 1, 3 and 6 months using a lay translation of the House Brackmann facial grading scale
Timepoint [6] 314562 0
One, three and six months post randomisation
Secondary outcome [7] 314563 0
Quality of Life: Emotional and functional wellbeing of the participant assessed by the parent/guardian and participant using the Pediatric Quality of Life Inventory scale
Timepoint [7] 314563 0
One, three and six months post randomisation
Secondary outcome [8] 314564 0
Pain assessed using child assigned visual analogue scale or Faces Pain Scale Revised (for participants aged 5 and older) and using parent assigned VAS for participants at any age. Pain scales are numbered 0 to 10
Timepoint [8] 314564 0
One, three and six months post randomisation
Secondary outcome [9] 314565 0
Prevalence of sykinesis or autonomic dysfunction using the Sunnybrook scale augmented by a synkinesis assessment questionnaire, assessed by a specialist clinician and/or research assistant
Timepoint [9] 314565 0
One, three and six months post randomisation
Secondary outcome [10] 314566 0
Health utilisation costs assessed via Child Health Utility 9D and via capture of cost information from the parent/guardian/participant related to in-patient, out-patient, or ED visits and to any other health facilities including general practitioner attendance for treatment or investigation
Timepoint [10] 314566 0
6 months following randomisation
Secondary outcome [11] 314710 0
Quality of Life: Emotional and functional wellbeing of the participant assessed by the parent/guardian and participant using the Child Health Utility 9D scale and sections of the Harter scale
Timepoint [11] 314710 0
One, three and six months post randomisation
Secondary outcome [12] 314711 0
Quality of life: Emotional and functional wellbeing of the participant assessed by the parent/guardian and participant using sections of the Harter scale
Timepoint [12] 314711 0
One, three and six months post randomisation

Eligibility
Key inclusion criteria
Patients must be aged between 6 months to less than 18 years, weigh greater than or equal to 5kg, be diagnosed with Bell's Palsy by their treating doctor and have an acute onset of symptoms of Bell's palsy for less than 72 hours prior to randomisation
Minimum age
6 Months
Maximum age
18 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Previous episode of Bell's Palsy or previously randomised in BellPIC study
- Contraindication to prednisolone: active or latent tuberculosis, systemic fungal infection, known hypersensitivity to prednisolone, diminished cardiac function, diabetes mellitus, peptic ulcer or chronic renal function, multiple sclerosis or recent active herpes zoster or chickenpox
- current use of systemic or inhaled steroid, or use within 2 weeks prior to the onset symptoms
- current or past oncological diagnosis
- FBE result (if obtained during this illness) may indicate leukaemia
- Pregnancy and/or lactating
- Currently receiving medications for which prednisolone is contraindicated
- Immunisation with a live vaccine within the previous 1 month
- Requirement for live vaccine within 6 weeks of first dose of prednisolone
- Signs of upper motor neuron VII nerve palsy (weakness of lower half of the face only)
- Current or recent (1 week prior to Bell's palsy symptoms) otitis media
- Evidence of vesicles on the ear from or vesicles/ulcers elsewhere on the body suggestive of recent herpes simplex, herpes zoster or chickenpox
- Known significant facial trauma within 1 week prior to symptoms appearing
- Referred to GP clinic in Emergency Department or failed to wait
- Unable to attend a follow up visit in one month time
- Any other condition at risk of being influenced by study treatment or completion of study
- Parents will not be able to comply with the study, or have enough understanding of the study.


Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
in the event of a child being diagnosed with Bell's palsy, a senior doctor from the ED or a member of the resarch team will review the medical history for initial determination of eligibility. They will then approach the potential participant to explain the study to them, and conduct the informed consent process.
Once written informed consent has been obtained, demographic information and medical history will be elicited. Study eligibility will be confirmed and the patient will be randomised.
To randomise the patient, the senior doctor or the research team will select the lowest number study pack. This study pack will either contain prednisolone or placebo made up by the central study pharmacist according to a computer generated randomisation schedule.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Participants will be randomised stratified by site in a 1:1 ratio to one of two treatment arms: intervention (prednisolone) or matched placebo.
An independant statistician will generate a randomisation schedule using variable block sizes, stratified by site.
This schedule will be used by the central phyarmacist at RCH to undertake the blinding, labelling and distribution of the study drugs to participating sites by putting together study packs of the required drug labelled with sequential study numbers for each site.
Randomisation at the site will be undertaken at the site by the doctor or research team by selecting the lowest numbered study pack (next pack system) from the study drug store in the ED
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Sample size estimation:
The primary outcome is the proportion of subjects who have complete recovery at 1 month post randomisation. Based on our observational data, we expect 60% of children without prednisolone to have complete recovery at 1 month. A study in adults found an improvement of 12% with prednisolone compared with placebo which was deemed to represent a clinically important difference.
To enable us to identify an increase in recovery from 60% to 72% or larger with 80% power requires a study with 244 subjects in each treatment group based on a two-sided test with a=0.05. Hence we aim to recruit 270 per group (540 in total) to allow for 10% loss to follow-up at 1 month.
Statistical Analysis:
Data will be analysed on an intention-to-treat basis where primary outcome data are available.
Primary outcome will be presented as a difference in proportions in each treatment group, with a comparison between the groups presented as a difference in proportions and as an odds ratio from a logistic regression model adjusted for site, with a 95% CI and p-value.
Secondary outcomes will be summarised by treatment group. Binary outcomes will be presented as proportions, with comparisons betwen the groups presented as a difference in proportions and as odds ratios from logistic regression adjusted for site, with 95% CIs and p-values.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,WA,VIC
Recruitment hospital [1] 3766 0
The Royal Childrens Hospital - Parkville
Recruitment hospital [2] 3767 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment hospital [3] 3769 0
The Children's Hospital at Westmead - Westmead
Recruitment hospital [4] 3771 0
John Hunter Children's Hospital - New Lambton
Recruitment hospital [5] 3772 0
Womens and Childrens Hospital - North Adelaide
Recruitment hospital [6] 3773 0
Princess Margaret Hospital - Subiaco
Recruitment hospital [7] 3774 0
Lady Cilento Children's Hospital - South Brisbane
Recruitment hospital [8] 5817 0
Gold Coast Hospital - Southport
Recruitment hospital [9] 7700 0
The Townsville Hospital - Douglas
Recruitment hospital [10] 7701 0
Logan Hospital - Meadowbrook
Recruitment postcode(s) [1] 9641 0
3052 - Parkville
Recruitment postcode(s) [2] 9642 0
3168 - Clayton
Recruitment postcode(s) [3] 9644 0
2145 - Westmead
Recruitment postcode(s) [4] 9646 0
2305 - New Lambton
Recruitment postcode(s) [5] 9647 0
5006 - North Adelaide
Recruitment postcode(s) [6] 9648 0
6008 - Subiaco
Recruitment postcode(s) [7] 9649 0
4101 - South Brisbane
Recruitment postcode(s) [8] 13269 0
4215 - Southport
Recruitment postcode(s) [9] 15623 0
4814 - Douglas
Recruitment postcode(s) [10] 15624 0
4131 - Meadowbrook
Recruitment outside Australia
Country [1] 6867 0
New Zealand
State/province [1] 6867 0
Auckland

Funding & Sponsors
Funding source category [1] 291239 0
Government body
Name [1] 291239 0
National Health and Medical Research Council
Address [1] 291239 0
16 Marcus Clarke Street
Canberra
ACT 2601
Country [1] 291239 0
Australia
Funding source category [2] 296000 0
Charities/Societies/Foundations
Name [2] 296000 0
Emergency Medicine Foundation
Address [2] 296000 0
2/15 Lang Parade Milton QLD 4064
Country [2] 296000 0
Australia
Primary sponsor type
Individual
Name
Franz Babl
Address
Murdoch Children's Research Institute
Flemington Road
Parkville
VIC 3052
Country
Australia
Secondary sponsor category [1] 289915 0
None
Name [1] 289915 0
Address [1] 289915 0
Country [1] 289915 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292797 0
The Royal Children's Hospital, Melbourne- Human Research Ethics Committee
Ethics committee address [1] 292797 0
Flemington Road
Parkville VIC 3052
Ethics committee country [1] 292797 0
Australia
Date submitted for ethics approval [1] 292797 0
Approval date [1] 292797 0
30/03/2015
Ethics approval number [1] 292797 0
35035A

Summary
Brief summary
Children diagnosed with Bell's palsy have a sudden weakness of facial muscles on one side of their face. Bell's palsy usually improves in children in about four to six weeks without treatment. However, in some children it may be a year before the facial weakness has completely resoved and in a small number of cases, the facial muscle weakness is permanent.
Recent research in adults with Bell's palsy has shown that a short course of treamtent with steroids (prednisolone) led to improved recovery time. Prednisolone is believed to reduce the irritation to the facial nerve. There are no similar studies in children and, because children's bodies respond different to adults', it is not known whether a short course of prednisolone will help children to recover more quickly. Currently, some doctors treat with prednisolone and others do not resulting in confusion and variability in medical care.

The study aims to answer the following question: In children presenting to Emergency Departments with recent onset of Bell's palsy, does treatment with prednisolone result in a higher proportion of children with recovery at 1 month compared with placebo.

Up to 13 hospitals in Australia and New Zealand will participate in enrolling 540 children/young people, aged 6 months to 18 years, who present to ED's within 72 hours of symptom onset.
Trial website
Trial related presentations / publications
1. Babl FE, Mackay MT,Borland ML, Herd DW, Kochar A, Hort J, Rao A, Cheek JA, Furyk J, Barrow L, George S, Zhang ,, Gardiner K, Lee KJ, Davidson A, Berkowitz R, Sullivan F, Porrello E, Dalziel KM, Anderson V, Oakley E, Hopper S, Williams F, Wilson C, Williams A, Dalziel SR; PREDICT (Paediatric Research In Emergency Departments International Collaborative) research network.
Bell's Palsy in Children (BellPIC): protocol for a multicentre, placebo-controlled randomized trial. BMC Pediatr. 2017 Feb 13;17(1):53. doi: 10.1186/s12887-016-0702-y.

2. Babl FE, Gardiner KK, Kochar A, Wilson CL, George SA, Zhang M, Furyk J, Thosar D, Cheek JA, Krieser D, Rao AS, Borland ML, Cheng N, Phillips NT, Sinn KK, Neutze JM, Dalziel SR; PREDICT (Paediatric Research In Emergency Departments International Collaborative).
Bell's palsy in children: Current treatment patterns in Australia and New Zealand. A PREDICT study. J Paediatr Child Health. 2017 Feb 8. doi: 10.1111/jpc.13463.
Public notes

Contacts
Principal investigator
Name 57078 0
A/Prof Franz Babl
Address 57078 0
Emergency Research Department
Murdoch Childrens Research Institute
Royal Children's Hospital
Flemington Road
Parkville VIC 3052
Country 57078 0
Australia
Phone 57078 0
+61399366748
Fax 57078 0
Email 57078 0
franz.babl@rch.org.au
Contact person for public queries
Name 57079 0
A/Prof Franz Babl
Address 57079 0
Emergency Research Department
Murdoch Childrens Research Institute
Royal Children's Hospital
Flemington Road
Parkville VIC 3052
Country 57079 0
Australia
Phone 57079 0
+61399366748
Fax 57079 0
Email 57079 0
franz.babl@rch.org.au
Contact person for scientific queries
Name 57080 0
A/Prof Franz Babl
Address 57080 0
Emergency Research Department
Murdoch Childrens Research Institute
Royal Children's Hospital
Flemington Road
Parkville VIC 3052
Country 57080 0
Australia
Phone 57080 0
+61399366748
Fax 57080 0
Email 57080 0
franz.babl@rch.org.au

No data has been provided for results reporting
Summary results
Not applicable