Children’s anti-inflammatory reliever study, United Kingdom (CARE-UK)
| ISRCTN | ISRCTN65432808 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN65432808 |
| IRAS number | 1009041 |
| Secondary identifying numbers | 23SM8661, IRAS 1009041, CPMS 59444 |
- Submission date
- 27/01/2024
- Registration date
- 19/11/2024
- Last edited
- 16/01/2025
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Respiratory
Plain English Summary
Background and study aims
This study aims to see if a new type of asthma reliever inhaler reduces asthma attacks in children. Children who have asthma attacks are treated with reliever medications (blue inhalers), which act quickly to briefly open the airways when they become narrow but their effect soon wears off. These blue inhalers don't treat the underlying problem, airway inflammation (swelling). Asthma attacks can be prevented with an inhaled steroid treatment (usually brown/purple inhalers which prevents the underlying airway swelling), a maintenance treatment. This new type of combination reliever inhaler contains a fast-acting steroid working by helping to dampen inflammation and is usually taken regularly/every day. In adults and teenagers, this inhaler has been shown to work well by relieving symptoms and treating the underlying airway inflammation resulting in fewer asthma attacks. This combination inhaler can be used instead of the usual reliever medication on its own for people with infrequent asthma symptoms or as both a regular preventer and a reliever for those with more troublesome symptoms.
Who can participate?
Children aged ≥6 to <12 years
What does the study involve?
Children will be randomly allocated to one of 2 groups:
1. Usual care, no change in treatment
2. The new approach, using the combination inhaler on its own as a reliever when symptoms occur or for both maintenance and reliever treatment
This study will identify children through GP records, and attendance at hospital asthma clinics or they may self-refer through social media adverts. Once they have agreed to take part in the study, the study team will ask that they attend 4 visits in total, some face-to-face, some over the telephone, and some in person at their local study site. The study will see which group has the most asthma attacks requiring a course of steroid tablets. The results of the trial will change National asthma guidelines and findings may be shared by Asthma and Lung UK on their platforms.
What are the possible benefits and risks of participating?
Children in both groups of the study will have access to the study team, who will make sure parents and children know how to take their inhalers, have an up-to-date Personal Asthma Action Plan and know when to seek help. It is hoped that those in the intervention group will find it easier to have just one inhaler to use.
If the child is on the intervention arm, using the combination inhaler, there may be a period where the child will need to adjust to the new inhaler. The schools will have to get used to the revised Asthma Action Plan as the number of puffs of the new reliever inhaler will be different to the number of puffs of the blue reliever inhaler. Detailed directions will be sent to the schools about students who are taking part in the trial and their new Personalised Asthma Action Plan. Parents will also be encouraged to review the new Personalised Asthma Action Plan closely with the children's teachers to ensure everyone in contact with the child is aware of the change of plans.
The new combination inhaler contains steroids which can affect growth. The study will measure height at the onset of the study and the end. Some children will be given an electronic monitoring device for their inhalers so the study team can keep track of how much medicine they have taken. For all children, prescription records will be checked so that inhaled steroid doses and courses of oral steroids can be compared in each group. The risk burden is fairly low for these patients and the long-term benefits of controlled asthma, and hence reduction in asthma attacks needing a course of steroids, outweigh the potential side effects.
Where is the study run from?
Imperial College London, UK
When is the study starting and how long is it expected to run for?
June 2023 to February 2027
Who is funding the study?
National Institute for Health and Care Research (NIHR), UK
Who is the main contact?
Dr Keith Boland, k.boland@imperial.ac.uk
Contact information
Scientific
Room 221. Level 2, Medical School Building, Norfolk Place
London
W2 1PG
United Kingdom
| Phone | +44 (0)20 7594 9480 |
|---|---|
| k.boland@imperial.ac.uk |
Principal Investigator
Praed Street
London
W2 1NY
United Kingdom
| Phone | +44 (0)20 7352 8121 ext 2938 |
|---|---|
| L.Fleming@rbht.nhs.uk |
Study information
| Study design | Randomized controlled open-label parallel-group study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | GP practice, Home, Hospital, Medical and other records, School |
| Study type | Safety, Efficacy |
| Scientific title | A novel reliever strategy for children with asthma: children’s anti-inflammatory reliever study, United Kingdom (CARE-UK) |
| Study acronym | CARE-UK |
| Study hypothesis | To determine the clinical effectiveness of budesonide-formoterol reliever therapy either alone or as part of maintenance and reliever therapy (MART) compared with SABA reliever therapy either used as monotherapy or with the child’s usual maintenance treatment in children with asthma aged ≥ 4years - < 12 years old. 1. To determine the clinical efficacy of budesonide-formoterol reliever therapy either AIR alone or as part of MART compared to usual care 2. To determine the safety of budesonide-formoterol reliever therapy either AIR alone or as part of MART 3. To determine the cost-effectiveness of budesonide-formoterol reliever therapy either AIR alone or as part of MART compared to usual care |
| Ethics approval(s) |
Approved 10/09/2024, Wales REC 5 (Castlebridge 4, 15-19 Cowbridge Road East, Cardiff, CF11 9AB, United Kingdom; +44 (0)2922 940910; Wales.REC5@Wales.nhs.uk), ref: 24/WA/0046 |
| Condition | Paediatric asthma |
| Intervention | Randomisation If the child is eligible for the study they will be randomised. A computer-generated randomisation list will be created and allocation concealed using an online system (OpenClinica). Stratified block randomisation will be used. The randomisation will be stratified by: a. Site b. Current GINA treatment step (see ‘Dosing Regimen’ below for more details) The study is open-label. Blinding is not being performed in order to maintain the potential real-world advantage of ICS-formoterol as a reliever. Control (Standard Care) Arm Patients in the control arm will continue with their current standard treatment as prescribed by their usual healthcare provider. This will be one of either: • SABA: A short-acting bronchodilator that provides immediate relief for asthma symptoms. • ICS: An inhaled corticosteroid that can be used as maintenance therapy. • ICS-LABA: A combination of an inhaled corticosteroid and a long-acting bronchodilator that can be used as a controller therapy or for reliever therapy. Intervention Arm Patients in the intervention arm will be issued two budesonide-formoterol (Symbicort®) 100/3 MDIs and a compatible spacer device such as Aerochamber Plus. One for home, maintenance and reliever doses, and the other to be kept at school for reliever use. Dose Regimen In clinical practice, treatment is stepped up and down depending on clinical control in terms of symptoms and risk of an asthma attack. Stepping up and down will be determined by the patient’s usual healthcare provider. For those in the intervention arm participants will increase or decrease the number of maintenance budesonide-formoterol puffs per day. The control arm will continue as per usual clinical care whereby the ICS dose is increased or decreased and additional controllers such as LABAs are added or removed depending on clinical control. The starting dose for budesonide-formoterol will be based on the dose of usual care inhaled corticosteroid ((ICS) low, medium or high) prescribed in the past 4 weeks as per current Global Initiative for Asthma (GINA) guidance: For paediatric low-dose, moderate-dose and high-dose for budesonide-formoterol: Beclomethasone dipropionate (ICS): Standard particle CFC free inhalers: 100 - 200mcg/day; >200 - 400mcg/day; >400 - mcg/day Extra-fine particle CFC free inhalers: 50 - 100mcg/day; >100 - 200mcg/day; >200 - mcg/day Budesonide: Metered dose and dry powder inhalers:100 - 200mcg/day; >200 - 400mcg/day; >400 mcg/day Fluticasone propionate: Metered dose and dry powder inhalers: 100mcg/day; 150 – 200mcg/day; >200 mcg/day |
| Intervention type | Drug |
| Pharmaceutical study type(s) | Dose response, Pharmacoeconomic, Prophylaxis, Therapy |
| Phase | Phase III |
| Drug / device / biological / vaccine name(s) | budesonide-formoterol (Symbicort) [budesonide, Formoterol fumarate dihydrate] |
| Primary outcome measure | Rate of severe asthma attacks: The rate of severe asthma attacks per patient per year, defined as worsening symptoms leading to an urgent medical review resulting in the prescription of systemic corticosteroids, measured at 52 weeks |
| Secondary outcome measures | 1. Rate of total asthma attacks: The rate of total asthma attacks per patient per year, defined as worsening symptoms leading to an urgent medical review, whether or not systemic corticosteroids are prescribed, measured at 52 weeks 2. Time to first severe attack: Time to first severe asthma attack measured in weeks from baseline over the 52-week study period 3. Proportion of participants with severe attacks: Proportion of participants experiencing at least one severe asthma attack, measured at 52 weeks 4. Days lost from school: Number of days lost from school due to asthma, measured annually 5. Days lost from work for childcare: Number of days lost from work due to caring for a child with asthma, measured annually 6. Change in Childhood Asthma Control Test (cACT): Change in cACT scores measured from baseline to 52 weeks 7. Change in Paediatric Asthma Quality of Life Questionnaire (PAQLQ): Change in PAQLQ scores measured from baseline to 52 weeks 8. Growth during the study period: Change in height from baseline to study completion at 52 weeks 9. Total ICS dose: Total inhaled corticosteroid (ICS) dose as measured by an electronic monitoring device or prescription records at 52 weeks 10. Total systemic corticosteroid dose: Total dose of systemic corticosteroids prescribed over 52 weeks 11. Change in Child Health Utility (CHU9D): Change in CHU9D scores measured from baseline over the course of the 52-week study 12. Quality Adjusted Life Years (QALYs): QALYs calculated as the area under the CHU9D curve over 52 weeks 13. Cost of asthma-related healthcare: Total cost of asthma-related healthcare utilization measured over 52 weeks |
| Overall study start date | 01/06/2023 |
| Overall study end date | 28/02/2027 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Child |
| Lower age limit | 6 Years |
| Upper age limit | 12 Years |
| Sex | Both |
| Target number of participants | 1352 |
| Participant inclusion criteria | 1. Clinician diagnosis of asthma 2. Children aged ≥ 6 to <12 years 3. Washout period of 6 months post previous IMP studies 4. Prescribed asthma medication in the past 6 months (SABA, ICS or ICS+LABA) 5. Parent or caregiver able to understand the study requirements and willing to provide informed consent |
| Participant exclusion criteria | 1. Other chronic airway diseases including but not limited to bronchiectasis, cystic fibrosis, sickle cell disease 2. Already using ICS-formoterol as a reliever Children on step 5, very high dose treatment (e.g. high dose ICS/LABA, prescription of biological therapy such as omalizumab) |
| Recruitment start date | 01/12/2024 |
| Recruitment end date | 01/08/2025 |
Locations
Countries of recruitment
- England
- Scotland
- United Kingdom
- Wales
Study participating centres
London
WC1N 3JH
United Kingdom
London
E1 1BB
United Kingdom
De Crespigny Park
Denmark Hill
London
SE5 8AB
United Kingdom
London
SW17 0QT
United Kingdom
London
SE1 7EH
United Kingdom
Leicester
LE1 5WW
United Kingdom
Nottingham
NG7 2UH
United Kingdom
Cambridge
CB2 0QQ
United Kingdom
Norwich
NR4 7UY
United Kingdom
Oxford
OX3 0AG
United Kingdom
Birmingham
B4 6NH
United Kingdom
Stoke-on-Trent
ST4 6QG
United Kingdom
Brighton
BN2 5BE
United Kingdom
Upper Maudlin Street
St Michael's Hill
Bristol
BS2 8BJ
United Kingdom
Liverpool
L14 5AB
United Kingdom
Manchester
M13 9WL
United Kingdom
Newcastle upon Tyne
NE1 4LP
United Kingdom
Clarendon Wing
Leeds
LS1 3EX
United Kingdom
Sheffield
S10 2TH
United Kingdom
Tremona Road
Southampton
SO16 6YD
United Kingdom
Cardiff
CF14 4XW
United Kingdom
Aberdeen Royal Infirmary
Foresterhill Road
Aberdeen
AB25 2XE
United Kingdom
Glasgow
G51 4TF
United Kingdom
Sponsor information
University/education
1 Floor Stadium House 68 Wood lane
London
W12 7RH
England
United Kingdom
| Phone | +44 (0)79 2850 2347 |
|---|---|
| k.danois@imperial.ac.uk | |
| Website | https://www.imperial.ac.uk/ |
"ROR" |
https://ror.org/041kmwe10 |
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
Results and Publications
| Intention to publish date | 28/02/2028 |
|---|---|
| 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. Peer reviewed scientific journals 2. Internal report 3. Conference presentation 4. Publication on website 5. Other publication We will ensure the data is disseminated as widely as possible, both via scientific publications and at conferences, but also via our patient and public representatives who are co-applicants (Asthma and Lung-UK). We will disseminate the results using Asthma and Lung UK's website and social media platforms and also via Imperial College website and social media platforms. |
| IPD sharing plan | The data-sharing plans for the current study are unknown and will be made available at a later date |
Editorial Notes
16/01/2025: Internal review.
20/06/2024: ISRCTN received notification of combined HRA/MHRA approval for this trial on 20/06/2024
29/01/2024: Study's existence confirmed by Health Research Authority (HRA) (UK).
