Prophylactic antibiotics to prevent chest infections in children with neurological impairment
| ISRCTN | ISRCTN71955516 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN71955516 |
| EudraCT/CTIS number | 2019-001508-39 |
| IRAS number | 263255 |
| Secondary identifying numbers | CPMS 44576, IRAS 263255, ACTRN12619001597189, Grant Code: 16/17/01 |
- Submission date
- 03/02/2020
- Registration date
- 22/04/2020
- Last edited
- 20/01/2025
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Nervous System Diseases
Plain English Summary
Background and study aims
Neurological Impairment (NI) can be any disorder of the body’s nervous system and can present with a range of symptoms. Many children with NI are prone to chest infections, which can lead to long stays in hospital, and can be life-threatening. Despite the impact on children and their families due to these infections and the high cost to health services, there is very little information on how best to prevent them. Some doctors prescribe long-term antibiotics but it is not known whether this makes any difference to the number of chest infections children suffer from, or whether these antibiotics can cause long-term harm. This study is looking at an antibiotic called azithromycin and aims to find out whether 12 months of treatment with azithromycin reduces how often children with NI have to stay in hospital with chest infections.
Who can participate?
Children and young people with NI aged 3-17 years
What does the study involve?
If interested in participating in the study, the caregiver/young person or child will be asked to sign a consent/assent form to confirm this in writing. Once the form is signed, the caregiver will be asked some questions about their child’s respiratory health and the site research team will check that the trial remains suitable before starting treatment. Before the participant starts their treatment of either azithromycin or placebo (dummy drug), information will be collected about them, including medical history and school attendance. Their weight will also be recorded and the caregiver will be asked to complete some questionnaires. Once the participant’s treatment is dispensed, they will go home and complete the sleep assessment(s). After this has been completed the participant will start their treatment at home. The treatment will be given once daily every Monday, Wednesday and Friday for 12 months and neither the participant, their caregiver or the local clinical team looking after them will know if they are taking azithromycin or placebo. During the 12 months, the site research team will be in touch with the caregiver each month to ask how their child is getting on and if, for example, they have been to see their GP. Usually, this will be by phone or email, however, every 3 months this will be face-to-face so the site research team can provide the caregiver with more of their child’s treatment, answer some questionnaires and record their child’s weight. The site research team will try to make these face-to-face follow-ups as easy as possible, for example, by arranging them at the same time as normal clinic visits where possible. There may be an additional face-to-face follow-up visit at 20 months, which will follow a similar format as the other face-to-face follow-up visits. If the participant does not take part in this additional visit, the site research team will ring the caregiver 28 days after their child finishes taking the treatment to check how their child has been since treatment stopped. In addition, if the participant visits their hospital outside of the arranged follow-up visits due to a chest infection, the site research team will also collect some information about this visit.
What are the possible benefits and risks of participating?
Azithromycin is used widely for the treatment of childhood infections. Children and young people who are given azithromycin may benefit from having fewer chest infections. There are very few side effects expected with azithromycin, though some children/young people may get mild diarrhoea and stomach pains and may feel sick (nausea) or be sick (vomit) when they first start taking azithromycin. Other side effects may include headache and feeling dizzy. There is a small chance that azithromycin may cause a rash or hearing problems. For those who are given the placebo there would be no higher risk than taking the antibiotics. If anyone who would like to take part is already taking antibiotics to prevent getting chest infections, then they would need to stop their antibiotics 13 weeks before entry into the trial. It is possible that during this period their respiratory symptoms might worsen. It is hoped that the results from the trial will help doctors and patients in the future when making decisions about treatment.
Where is the study run from?
University of Liverpool (UK)
When is the study starting and how long is it expected to run for?
March 2019 to June 2024
Who is funding the study?
1. National Institute for Health Research HTA Programme (UK)
2. National Health and Medical Research Council (NHMRC) (Australia)
Who is the main contact?
Helen Eccleson
parrot@liverpool.ac.uk
Contact information
Scientific
Alder Hey Children’s NHS Foundation Trust
University of Liverpool
Institute in The Park
Alder Hey Children’s Hospital
Eaton Road
Liverpool
L12 2AP
United Kingdom
 ORCID ID |
0000-0002-7055-6034 |
|---|---|
| Phone | +44 (0)151 794 9838 |
| parrot@liverpool.ac.uk |
Study information
| Study design | Randomized; Interventional; Design type: Treatment, Drug |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Participant information will be made available via the PARROT website: http://www.parrot-trial.org.uk. Please note that the website is not yet live but will be before recruitment starts. |
| Scientific title | Joint UK and Australia multicentre, randomised, double-blind, placebo-controlled pragmatic trial comparing 52 weeks of azithromycin to placebo in children with neurological impairment at risk of lower respiratory tract infection (the PARROT trial) |
| Study acronym | PARROT |
| Study hypothesis | To determine whether 52 weeks of azithromycin prophylaxis is more effective than placebo in reducing the proportion of children and young people with non-progressive neurological impairment admitted to hospital with lower respiratory tract infections. |
| Ethics approval(s) | Approved 23/03/2020, North West - Liverpool Central Research Ethics Committee (3rd Floor, Barlow House, 4 Minshull Street, Manchester, M1 3DZ, UK; +44 (0)2071048387, +44 (0)207 104 8056; liverpoolcentral.rec@hra.nhs.uk), REC ref: 20/NW/0047 |
| Condition | Neurological impairment |
| Intervention | PARROT will be a joint UK and Australian multicentre trial. The primary objective is to determine whether 52 weeks of azithromycin prophylaxis is more effective than placebo in reducing the proportion of children with non-progressive NI admitted to hospital with LRTI. Study participants will be randomised to either 52 weeks prophylactic azithromycin or placebo in a 1:1 ratio. Both patients and their healthcare teams will be blinded to treatment allocation. Taking part in the trial will involve phone or email follow-up every month and face-to-face visits every 3 months over a 12 month (52 week) period. Study tests include questionnaires, weight and nasal swabs*. Initial visit will involve the assessment of eligibility criteria, including calculation of the LRSQ score, following consent. Once eligibility has been confirmed by a delegated medical practitioner, the patient can be randomised. The baseline visit will measure weight, assess if the patient is taking any concomitant medications and whether they have recently received any vaccinations and will review recent medical history. A series of questionnaires will be completed by the parent/caregiver and by the patient (if capacity allows). A nasal swab* will also be taken at this visit. Sleep actigraphy will be completed after randomisation, but prior to treatment administration. Study medication will be dispensed at this visit. Participants will be contacted via email/phone at 1, 2, 4, 5, 7, 8, 10 and 11 months. An assessment of safety events, concomitant medication and changes to respiratory treatment and review of GP, A&E attendances and hospital admissions will be undertaken. Participants will attend a face-to-face visit at 3, 6 and 9 months. In addition to the assessments performed at the email/phone visits, the parent/caregiver and participant (if capacity allows) will complete study questionnaires and return the completed treatment diary. The participants weight and relevant interventions will also be documented. Study medication will also be dispensed at these face-to-face visits. A nasal swab* will be taken at the 6-month visit. Participants will also attend a face-to-face end of study visit at 12 months. In addition to the assessments performed at the face-face-visits, there will be a review of vaccinations and the sleep assessment(s) the parent/caregiver completed at the start of the study will be completed again just before this visit. This is also when treatment finishes and no more treatment will be dispensed. A nasal swab will also be taken at this visit*. An additional face-to-face visit will take place at 20 months if recruitment to the trial is still ongoing. Assessments will be the same as those undertaken for the 12-month visit, excluding the sleep assessments and actigraphy. For participants that will not have a 78-week follow-up visit scheduled (as detailed above), a follow-up phone call at 28 days post-treatment will be completed to assess safety events only. If a participant is hospitalised outside of their arranged follow-up visit due to a chest infection, additional information will be collected about this visit and a cough and nasal swab* will be collected. Parents of children with neurological impairment were involved in all stages in the development of this trial. PPI informed the recruitment strategy, inclusion and exclusion criteria and added to the outcomes of the trial. Parent advisors will continue to have a crucial role in ensuring the trial addresses the needs and concerns of families of children with neurological impairment, and information from the trial is made available in formats they find useful. *As outlined in the protocol, swabs will be taken for Australian participants only. An amendment will be submitted to include swabs for UK participants once contractual arrangements are in place. |
| Intervention type | Other |
| Primary outcome measure | Proportion of children and young people (3-17 years) hospitalised* at their recruiting or designated centre with Lower Respiratory Tract Infection (LTRI) over the 52-week intervention period, recorded at 4, 8, 13, 17, 21, 26, 30, 34, 39, 43, 47 and 52 weeks *Hospitalisation includes those who are admitted to hospital for only a short period with LTRI e.g. 12 hours and go home with a course of antibiotics. However, if participants are hospitalised again within 2 weeks of the initial admission, this will be classified as the same event |
| Secondary outcome measures | 1. Health-related QoL of child and parent/carer measured using parent QoL assessment (Warwick-Edinburgh Mental Wellbeing Scale) and patient QoL assessment (DISABKIDS) at baseline, 13, 26, 39 and 52 weeks 2. Safety events, tolerability and adherence measured by the assessment of adverse events and withdrawals from study treatment at 4, 13, 17, 21, 26, 30, 34, 39, 43, 47 and 52 weeks, and treatment diary at 13, 26, 39 and 52 weeks 3. Respiratory medication usage assessed by reviewing concomitant medication which could impact the respiratory system at baseline, 4, 8, 13, 17, 21, 26, 30, 34, 39, 43, 47 and 52 weeks, and vaccinations at baseline and 52 weeks 4. Weight based on World Health Organisation z-scores using WHO Anthro calculator (https://www.who.int/growthref/tools/en) assessed at baseline, 13, 26, 39 and 52 weeks 5. Quality/amount of parent and child/young person’s sleep measured using the primary caregiver sleep actigraphy and corresponding primary caregiver sleep log (UK only), the Child’s Sleep Habits Questionnaire and 1 week patient sleep diary at baseline and 52 weeks 6. Respiratory symptoms measured using LRSQ-Neuro score and the respiratory symptom questionnaire at baseline, 13, 26, 39 and 52 weeks, and changes to respiratory treatments/support and surgical/other interventions at 13, 26, 39 and 52 weeks 7. Number, duration and severity of LRTI; time to first LRTI is measured by reviewing the occurrence of chest infection and LRTI, changes to respiratory treatments/support and the assessment of adverse events at 4, 8, 13, 17, 21, 26, 30, 34, 39, 43, 47 and 52 weeks; by using the resource use questionnaire at baseline, 13, 26, 39 and 52 weeks and documenting length of stay in hospital, admission to PICU/HDU and changes to respiratory treatments/support for any unscheduled visits 8. Unscheduled medical presentations (GP visits and A&E attendances) for LRTI measured by reviewing medical history at baseline; reviewing the occurrence of chest infections and LRTIs and the assessment of adverse events at 4, 8, 13, 17, 21, 26, 30, 34, 39, 43, 47 and 52 weeks, and using the resource use questionnaire at baseline, 13, 26, 39 and 52 weeks 9. Use of other health and social care services, school attendance and indirect costs measured using the resource use questionnaire at baseline, 13, 26, 39 and 52 weeks and Hospital Episode Statistics (HES) at 52 weeks 10. Number of courses of ‘rescue’ antibiotics prescribed for LRTI measured by reviewing concomitant medications which could impact the respiratory system at baseline, 4, 8, 13, 17, 21, 26, 30, 34, 39, 43, 47 and 52 weeks 11. Quality-adjusted life years (QALY) measured using CHU9D and EQ-5D-Y at baseline, 13, 26, 39 and 52 weeks 12. Nasal swab for microbiology and resistance profiling taken at baseline, 26 and 52 weeks, and for unscheduled visits (for Australian participants only until UK contractual arrangements are in place) 13. Nasal swab/nasopharyngeal aspirate to investigate viral causes of acute LRTI (as defined by the protocol) and cough swab/sputum collection to investigate bacterial causes of acute LRTI (as defined by the protocol) taken at unscheduled visits (for Australian participants only until UK contractual arrangements are in place) 14. Residual impact of 52 weeks antibiotic prophylaxis assessed at 78 weeks, using the following measures: 14.1. Respiratory symptoms measured by assessing LRSQ-Neuro score, respiratory symptom questionnaire, changes to respiratory treatments/support and surgical and other interventions 14.2. Weight based on World Health Organisation z-scores using WHO Anthro calculator (https://www.who.int/growthref/tools/en) 14.3. Nasal swab for microbiology and resistance profiling 14.4. Changes in respiratory medication usage measured by reviewing concomitant medications which could impact the respiratory system and vaccinations 14.5. Number, duration and severity of LRTI; time to first LRTI measured using the resource use questionnaire and reviewing the occurrence of chest infection and LRTI , changes to respiratory treatments/support and the collection of adverse events 14.6. Quality-adjusted life years (QALY) measured using the CHU9D and EQ-5D-Y 14.7. Use of other health and social care services, school attendance and indirect costs measured using Hospital Episode Statistics (HES) 14.8. Health-related QoL of child and parent/carer measured using the patient QoL assessment (DISABKIDS) and parent QoL assessment (Warwick-Edinburgh Mental Well-being Scale) 14.9. Unscheduled medical presentations (GP visits and A&E attendances) for LRTI measured by reviewing the occurrence of chest infection and LRTI, the collection of adverse events and the resource use questionnaire 14.10. Number of courses of ‘rescue’ antibiotics prescribed for LRTI measured by reviewing concomitant medications which could impact the respiratory system 14.11. Safety events measured using the assessment of adverse events |
| Overall study start date | 01/03/2019 |
| Overall study end date | 04/06/2024 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Child |
| Lower age limit | 3 Years |
| Upper age limit | 17 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 500; UK Sample Size: 350 |
| Total final enrolment | 90 |
| Participant inclusion criteria | 1. Children and young people who are aged between 3-17 years at randomisation 2. Written informed consent from participant (or appropriate person if incapacitated / minor) 3. Participant (or appropriate person if incapacitated / underage) and caregiver have a good understanding of the English language 4. Diagnosed with non-progressive, non-neuromuscular NI* 5. Persistent respiratory symptoms** 6. One or more of the following: 6.1. Received at least 2 courses of oral antibiotics for LRTI in 52 weeks prior to eligibility 6.2. Have been hospitalised with a LRTI within 52 weeks prior to eligibility and completed 13 week ‘washout’ period (where applicable)*** 6.3. Prescribed prophylactic antibiotics for LRTIs and undergone a 13 week ‘washout’ period*** * Most will likely have cerebral palsy. However, some children may have no formal diagnosis to account for their symptoms. ** Persistent respiratory symptoms defined by LRSQ-Neuro score of > = 95%CI for age *** Must have undergone a 13 week‘washout’ period where administered IV antibiotics during hospitalisation or have been previously prescribed and administered prophylactic or nebulised antibiotics |
| Participant exclusion criteria | 1. Any neuromuscular disorders including SMA, Duchenne muscular dystrophy etc., or neurological disorders in which progressive deterioration in neurological condition are known to occur (e.g. Rett syndrome, some neurometabolic syndromes) 2. Pre-existing non-neurological conditions that impact respiratory functions such as CF, immunodeficiency etc. Note: Children with NI known to have bronchiectasis will not be excluded 3. Known contra-indication to using or hypersensitivity to azithromycin, erythromycin, macrolide or ketolide antibiotic or to any of the excipients contained in the study drug 4. Use of macrolide antibiotics within 90 days prior to eligibility 5. Known significant hepatic disease (hepatic impairment per Child-Pugh classification C) 6. Treatment with ergot derivatives (dihydroergocristine, dihydroergotamine, dihydroergotoxine, nicergoline or a combination of dihydroergocryptine with caffeine) 7. Child/young person already taking prophylactic antibiotics for non-respiratory causes (e.g. UTIs) 8. Previously randomised in PARROT 9. Recruited to another IMP trial and continuing to administer the IMP |
| Recruitment start date | 18/03/2022 |
| Recruitment end date | 31/05/2023 |
Locations
Countries of recruitment
- Australia
- England
- Scotland
- United Kingdom
Study participating centres
Eaton Road
West Derby
Liverpool
L12 2AP
United Kingdom
Freeman Road
High Heaton
Newcastle-upon-Tyne
NE7 7DN
United Kingdom
Aldgate
London
E1 8DE
United Kingdom
Whitechapel
London
E1 1BB
United Kingdom
2 Eday Road
Aberdeen
AB15 6RE
United Kingdom
James Arrott Drive
Dundee
DD1 9SY
United Kingdom
2-4 Waterloo Place
Edinburgh
EH1 3EG
United Kingdom
Hamilton
ML3 0TA
United Kingdom
Hollyhurst Road
Darlington
DL3 6HX
United Kingdom
Marton Road
Middlesbrough
TS4 3BW
United Kingdom
Holdforth Road
Hartlepool
TS24 9AH
United Kingdom
Oxford Road
Manchester
M13 9WL
United Kingdom
Arrowe Park Road
Upton
CH49 5PE
United Kingdom
Chester
CH2 1UL
United Kingdom
Sheffield
S10 2TH
United Kingdom
Beckett Street
Leeds
LS9 7TF
United Kingdom
Sutton-in-Ashfield
NG17 4JL
United Kingdom
Queens Medical Centre
Derby Road
Nottingham
NG7 2UH
United Kingdom
Stoke-on-Trent
ST4 6QG
United Kingdom
Wolverhampton Road
Heath Town
Wolverhampton
WV10 0QP
United Kingdom
Blackshaw Road
Tooting
London
SW17 0QT
United Kingdom
London
SE5 9RS
United Kingdom
Guy's Hospital
Great Maze Pond
London
SE1 9RT
United Kingdom
Highpoint Venue
Bursledon Road
Southampton
SO19 8BR
United Kingdom
Taunton
TA1 5DA
United Kingdom
Metchley Park Road
Birmingham
B15 2TG
United Kingdom
Marlborough Street
Bristol
BS1 3NU
United Kingdom
Uttoxeter Road
Derby
DE22 3NE
United Kingdom
Headley Way
Headington
Oxford
OX3 9DU
United Kingdom
Duckworth Lane
Bradford
BD9 6RJ
United Kingdom
Luton
LU4 0DZ
United Kingdom
Pond Street
London
NW3 2QG
United Kingdom
Barrack Road
Exeter
EX2 5DW
United Kingdom
Infirmary Square
Leicester
LE1 5WW
United Kingdom
Stott Lane
Salford
M6 8HD
United Kingdom
Sponsor information
University/education
c/o Mr Alex Astor
Research Support Office
2nd Floor Block D Waterhouse Building
3 Brownlow Street
Liverpool
L69 3GL
England
United Kingdom
| Phone | +44 (0)151 794 8739 |
|---|---|
| sponsor@liv.ac.uk | |
| Website | http://www.liv.ac.uk/ |
"ROR" |
https://ror.org/04xs57h96 |
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
- Location
- United Kingdom
Government organisation / National government
- Alternative name(s)
- NHMRC
- Location
- Australia
Results and Publications
| Intention to publish date | 31/12/2024 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | 1. The protocol will be published on the funder (NIHR) website 2. Peer-reviewed scientific journals 3. Conference presentation 4. Publication on website 5. Submission to regulatory authorities |
| IPD sharing plan | The data-sharing plans for the current study are unknown and will be made available at a later date. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | No | No | ||
| Basic results | 20/01/2025 | No | No |
Additional files
Editorial Notes
20/01/2025: The basic results have been uploaded as an additional file.
16/01/2025: Total final enrolment added.
15/01/2025: The overall study end date has been changed from 31/12/2023 to 04/06/2024.
12/07/2024: The intention to publish date was changed from 01/12/2023 to 31/12/2024.
14/08/2023: The following changes have been made:
1. The recruitment end date has been changed from 24/04/2023 to 31/05/2023.
2. The overall study end date has been changed from 29/02/2024 to 31/12/2023.
13/03/2023: The recruitment end date has been changed from 31/08/2022 to 24/04/2023.
23/03/2022: The recruitment start date has been changed from 01/05/2020 to 18/03/2022.
21/03/2022: The following changes have been made:
1. The trial website has been added.
2. Birmingham Womens NHS Foundation Trust, University Hospitals Bristol and Weston NHS Foundation Trust, University Hospitals of Derby and Burton NHS Foundation Trust, Oxford University Hospitals NHS Foundation Trust, Bradford Teaching Hospitals NHS Foundation Trust, Bedfordshire Hospitals NHS Foundation Trust, Royal Free London NHS Foundation Trust, Royal Devon and Exeter NHS Foundation Trust, University Hospitals of Leicester NHS Trust and Northern Care Alliance NHS Foundation Trust have been added to the trial participating centres.
03/02/2020: Trial's existence confirmed by the NIHR.
