BellPIC. Bell s Palsy in Children Study

Transcription

1 BellPIC Bell s Palsy in Children Study

2 Bell s palsy in Children (BellPIC) Lead site: Royal Children s Hospital / Murdoch Children s Research Institute, Melbourne 10 PREDICT centres: Victoria: RCHM, Monash Medical Centre, Sunshine New Zealand: Starship Hospital Auckland NSW: Westmead Children s Hospitals; John Hunter Children s Hospital, Newcastle WA: Princess Margret Hospital, Perth QLD: Lady Cilento Children s Hospital, Brisbane, Gold Coast Hospital SA: Women s and Children s Hospital, Adelaide National Health and Medical Research Council (NHMRC) funded ($1,100,000)

3 What is Bell s Palsy? Sudden onset unilateral weakness of the facial muscles Caused by impairment of the peripheral facial (7 th ) nerve Cause unclear presumed idiopathic, immune mediated Hopkinsmedicine.org

4 What is Bell s Palsy? Facial nerve supplies: muscles of facial expression, taste tongue, muscles of hearing, salivary and lacrimal glands

5 What is NOT Bell s Palsy? Abnormality of the facial (7 th ) nerve due to other, known causes Facial trauma (history or signs of trauma) Otitis media (fever, pain, abnormal tympanic membrane) Herpes zoster (blisters in ear canal) Brain tumour or other central nervous processes => central (headaches, other neurological findings)

6 How to Differentiate Central vs Peripheral Facial (7 th ) Nerve Palsy? Peripheral 7 th palsy (such as Bell s palsy): Fibres for forehead cross over- so unable to wrinkle forehead on affected side Central 7 th palsy (such as due to brain tumour): Still able to wrinkle forehead on affected side

7 Bell s Palsy in Children 60% of children recover by 1 month (without steroids) >90% of children recover within 12 months HOWEVER these children suffer with issues such as, Prolonged functional impairment: Unable to close mouth > impacts eating and speech Eye closure/ drying Emotional impact of disfigured face & communication Problems after healing (synkinesis- misconnection of nerves) Crocodile tears or corneal drying Involuntary facial movement, facial spasm Pain

8 Bell s Palsy Treatment In adults there is high level evidence that Prednisolone improves recovery in Bell s palsy (and antivirals do NOT work) Two recent studies: 50 mg per d x 10 d, no taper, vs placebo 83% vs 63% recovery by 3 months Sullivan NEJM mg per d x 5 d, then taper x 5 d, vs placebo 62% vs 51% recovery by 3 months Engstrom Lancet Neuro 2008

9 Bell s Palsy Treatment - Children No similar high level data in children One RCT in children but no placebo, small numbers 1 mg/kg/d prednisolone equivalent x 10 days vs nil 86% vs 72% recovery at 4 months All patients fully recovered by 12 months Ünüvar Ped Neurology 1999 Almost all paediatric patients eventually recover Currently only 50% of children treated with prednisolone

10 Bell s Palsy Guidelines In adults: American Academy of Neurology (2012) Steroids have proven efficacy, no further studies needed In children: no published national or international guidelines RCH Melbourne: The role of steroids in Bell's palsy in children is unclear, however steroids appear to benefit adults, particularly if given < 72 hours and if complete palsy present. Prednisolone (1mg/kg/day PO daily for 10 days) may be considered for Bell's palsy presenting < 72 hours.

11 BellPIC Study Research question: Does PO prednisolone increase recovery from Bell s palsy in children at 1 month compared with placebo?

12 What is the BellPIC Study? Blinded placebo controlled trial Prednisolone 1 mg/kg (max 50 mg) vs placebo Children aged 6 mo to <18 yrs with Bell s palsy Emergency department only 270 children in each group (540 total) Over 4 year period at 10 centres

13 BellPIC Study Inclusion criteria: Aged 6 months to < 18 years Weight 5kg Be diagnosed with Bell s palsy by their treating doctor Have acute onset of symptoms of Bell s palsy for less than 72 hours prior to randomisation

14 Exclusion criteria:

15 BellPIC Primary outcome: Complete recovery per House-Brackmann scale at 1 month Will be assessed by a neurologist/specialist paediatrician/emergency consultant

16 BellPIC: Logistics Step 1: Inclusion/Exclusion Patient presents with facial weakness and is diagnosed with Bell s Palsy During hours Research team is notified, after hours, ED Doctor completes Retrieve CRF 1 from BellPIC box and ensure patient meets all inclusion criteria and no exclusion criteria

17 CRF 1 Ensure patient meets ALL inclusion criteria And NO exclusion criteria Instruct clinicians to follow these instructions

18 CRF 1 Instructions regarding consent process 2 separate consent packs: < 12 years: parent information and consent >12 years: parent consent & patient consent

19 Parent Information & Consent Form (PICF) Once parent has signed, photocopy this. Give the photocopied copy to the parents for their records and file the original in your BellPIC consent folder. Optional consent for photos/videos

20 BellPIC In Emergency Department What happens next. The doctor or RA will then pick up a study pack All study packs will be numbered in numerical order This number will correspond with the study drug pack So, if you pick up the pack RCH002, you would also pick up the mediation RCH002. This number becomes their randomisation/study number

21 BellPIC In Emergency Department CRF 2 All the instructions on how to complete the study can be found on CRF 2. Please familiarise yourself with CRF 2

22 CRF 2 Basic demographics and information about current illness

23 CRF 2 This is the House Brackmann (HB) facial grading scale. Instruct the Doctors to read carefully and choose which one they think suits the patient. We use the HB scale as our primary outcome (complete recovery from Bell s palsy = HB 1) Synkinesis is lighter as it is not usually apparent in the early phases of Bell s Palsy We are also asking the patient/parent what their perception of the facial weakness is. The HB Lay (specially designed in plain language for parents) should be provided to the parents and they should then choose a grade that suits their child

24 CRF 2 Provide this to the parent and allow sufficient time to read through and choose a grade. You may assist the family

25 CRF 2 The Sunnybrook Facial Grading System is a little more complicated than the HB scale. Instruct doctors to circle numbers in each section. The research team will then add up the scores later.

26 CRF 2 We require photos and videos of all children This will be reviewed by an independent neurologist who will decide a HB grade that will be compared against what the Dr chose See next slide for further information

27 Photos We require 4 poses: Eyes open (no expression) Smiling Eyes closed tightly, clenched Raised eyebrows Note: poses 2-4 are highly exaggerated and forced

28 Video Instructions For children who are able to follow commands: Please film the child completing the previous 4 poses Eyes open (no expression) Smiling Eyes closed tightly, clenched Raised eyebrows For children too young to follow commands: Please take a video of the child s face. We need to be able to see the level of palsy. The video should include the child actively trying to move their face. For example, smiling, laughing, opening mouth, closing eyes, crying, looking up (to raise eyebrows) or looking down. ** We need to capture the 4 poses above by asking the child to do things. Film as many times as you want, we can edit later. It is quite difficult to capture the child s face but We need to see general movement of the facial muscles ***Click on the video to play

29 CRF 2 The study drug will either be prednisolone or placebo. The placebo has been made by RediPRED so is identical to the prednisolone (just no active ingredient) The doctor must fill out this script (for legal reasons), this replaces the pharmacy script The patient needs 10 day supply, therefore Between 5kg to <25kg they need 2 bottles Over 25kg they need 4 bottles The RN/Dr who administers the dose should sign here to replace hospital medication chart

30 Study Participant card This will be printed on card paper and folded over It has all the instructions for the study on it and should remain with the participant/parent at all times

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32 What happens next? For the patient: Once they have been administered the first dose of study drug, the patient can be discharged The study team will call them in days to assess drug compliance, adverse events and recovery The patient will then return for a follow up visit at one month post randomisation This will either be with a neurologist/specialist paediatrician/emergency consultant

33 BellPIC Bell s Palsy in Children Study Follow Up

34 Emergency: CRF 1- Eligibility Criteria Bell s palsy in Children (BellPIC) Time Points CRF 2- Randomisation Form As soon as possible following ED presentation: CRF 3- Pt details & History of Presenting Illness CRF 4- ED Assessment days after ED presentation Follow up phone call 1 Month after ED presentation Follow up visit

35 Immediately following ED presentation In Emergency: Collect CRF 1 & CRF 2 from Emergency Complete dispensing log Ensure Patient Identification Sheet has been filled in Check study medications In the Office: Complete log book Enter CRF 1 & CRF 2 into RedCap database Upload photos/videos from ipod into database Also save onto secure hard drive as back up Delete photos from ipad and return to ED

36 Dispensing Log

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38 CRF 3: Pt details and History of Presenting Illness Will be entered directly into RedCAP by RA Information will be collected from EDIS (HAS) Patients medical record Any unknown information Write on page for follow up Ask parents in follow up phone call Paper copy of CRF available To be used until RedCAP up and running Treating doctor How difficult they found HB and Sunnybrook

39 CRF 4: ED Assessment Will be entered directly into RedCAP by RA Information will be collected from EDIS (HAS) Patients medical record Any unknown information Write on page for follow up Ask parents in follow up phone call Paper copy of CRF available To be used until RedCAP up and running Questions relating to treatment in ED Date and time seen, triage category, admission, discharge Tests conducted, Specialty reviews

40 Keeping track of Time Points Once patient is entered into RedCAP, the program will automatically generate dates in the calendar We have also created a tick list to put in the front of the patient s file:

41 CRF 5: Follow up phone call Completed days post ED presentation Main aims Assess drug compliance Assess recovery Adverse events Ensure patients do not throw out study drug Organize appointment for 1 month follow up Ask any questions that were unknown on previous CRF s

42 CRF 6: One Month Follow Up Visit Face to face meeting with participant Neurologist/ Emergency Consultant/ Specialist Paediatrician Research Nurse Different versions for different ages 6-24 months 2-3 years 4 years old 5-7 years 8-12 years years All have parent proxy versions if children are unable to complete

43 Timing of One Month Visit: Minimum of 28 days post randomisation, up to 35 days. In extreme circumstances, visits can be arranged between days if patients are unable to attend post 28 days.

44 CRF 6: One Month Follow Up Visit Preparation Organise room booking Double check clinician is available Ensure you have ipod for photos/videos Arrange car parking passes

45 Page 1-3 the same for all ages Ages listed here Collect study drugs and return to pharmacy

46 New Questions

47 To be completed by the clinician Primary Outcome

48 To be completed by the clinician Scores can be added after visit by Research Nurse

49 To be completed by the clinician in conjunction with the parent/participant

50 To be completed by the Research Nurse Photos and videos to be taken again Uploaded into RedCap following visit

51 To be completed by the Research Nurse in conjunction with the parent/participant Participants to use VAS/Faces age dependant Parents to use VAS

52 Questionnaires The questionnaires are all age dependent. *Younger ages do not have some questionnaires Instructions on how to complete questionnaires will all be found in the CRF 6 separate to questionnaire *talk parent/participant through instructions but allow them to fill in questionnaire independently Questionnaires include: Quality of Life PedsQL CHU9D Harter Appearance Scale

53 Quality of Life: PedsQL PedsQL is divided into the following age groups: 2-4 years (Parents to fill out) 5-7 years 8-12 years years (Participants to fill out) *** There are parent proxy versions for all these age groups as well if children are unable to fill them in

54 An example of the instructions

55 An example of the questionnaire (5-7 years) Only circle one option per line

56 Quality of Life: CHU9D CHU9D is divided into the following age groups: 5-7 Parent Proxy 8-18 to be filled in by the participant There are no CHU9D questionnaires before 5 years of age *** CHU9D is a new QOL scale that also collects health economic data

57 The explanations

58 9 questions in total Tick one answer per question

59 Harter Appearance Scale Harter is divided into the following age groups: Harter Pictorial: Ages 4-7 Divided further: 4-5 Boys & girls 5-7 Boys & girls Harter Children: 8-12 Harter Adolescent: * No scales for younger than 4 years old

60 Harter Pictorial Scale 4 different scales: 4-5 boys 4-5 girls 6-7 girls 6-7 boys The recording and scoring sheets are divided into age groups: 4-5 years old 6-7 years old This can be calculated at a later time

61 Instructions for the research nurse Instructions for the patient

62 The research nurse is to read out the question to the child while pointing to the appropriate picture The child then chooses which picture is most like them Then they choose if it is A LOT like them, or just A LITTLE bit like them The number used to score is in the circle on the RA page The child should only see the picture page, not the question This will be on a hard page/laminated spiral book

63 Children scale Adolescent scale

64 CRF 6 is now complete Thank the family for coming in to the 1 month follow up Provide family with a car park pass if applicable For those recovered (HB=1) Questionnaires will be sent out in the mail at 3 & 6 months For those not recoverd (HB 2-6) They will need to return for a 3 month follow up visit Ensure that if needed, the patient has been referred to an appropriate specialist

65 Following the One Month Visit (Primary Outcome) The involvement of the participant following the one month visit is entirely dependent on their recovery from the Bell s Palsy They are divided into two groups: - Recovered (HB=1) - Not recovered (HB 2-6)

66 Time Points: Recovered For children recovered at one month 3 & 6 month survey (via mail and phone)

67 Time Points: Not Recovered For children not recovered 3 month follow up visit (with RA) Recovered Not Recovered 6 month survey (via mail) 6 month follow up visit (with RA) Not Recovered 12 month survey

68 3 Month Follow Up: Non-Recovered Non recovered will come in for a Study Visit at 3 months - With the Research Nurse +/- Clinician CRF 7 to be completed - Identical to CRF 6 - Asks all the same questions - Same questionnaires - Photos and videos

69 3 Month Follow Up: Recovered Non recovered are required to complete a survey sent to them in the mail Comprises of two parts: 1. Send age appropriate survey to families - Contains cover letter, pain scale, HB Lay, PedsQL, CHU9D & Harter Appearance Scale - The letter will instruct the families to complete the surveys in preparation for phone call 2. Call the families - Aim is to see if symptoms have returned or gotten worse, assess HB Lay - If symptoms have returned, we ask further questions, ie. Hearing, lacrimation, altered taste, health economics questions etc - If still remain recovered, will go straight to questionnaires **Entered directly into RedCAP database- CRF 7

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72 Time Points: Not Recovered For children not recovered at 3 months 6 month follow up visit (with RA) Recovered Not Recovered End of participation in study 12 month survey

73 6 Month Follow Up Paperwork and procedure is the same as 3 month follow up CRF 8 used for non recovered patients at follow up visit 6 month surveys used for recovered patients ** Entered directly into RedCAP- CRF 8

74 12 Month Follow Up Only for patients NOT recovered at 6 months Will ask if they have recovered, and their recovery date. No questionnaires, no study visits.

75 Ethics Amendment/Modification RCH will submit a modification for the following - List Previous episode of Bell s Palsy as an exclusion criteria - Submit all letters and surveys to HREC for review