Can we reduce asthma attacks in children using exhaled nitric oxide measurements?
| ISRCTN | ISRCTN67875351 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN67875351 |
| Secondary identifying numbers | 34390 |
- Submission date
- 10/04/2017
- Registration date
- 12/04/2017
- Last edited
- 28/05/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Respiratory
Plain English Summary
Background and study aims
Asthma is a long-term condition which affects the airways. When a person is suffering from asthma, the airways are extremely sensitive (hyperresponsive) to both natural chemicals the body produces and irritants outside the body, such as dust or pollen. Coming into contact with these substances can cause an asthma attack (also known as an exacerbation), which involves feelings of tightness in the chest as the airways become inflamed (swollen), causing coughing, wheezing, chest tightness and difficulty breathing. Every year in the UK, 150,000 children see their family doctor for an asthma exacerbation and 25,000 are hospitalised. One third of the £1 billion NHS budget for asthma is spent on provision for unscheduled care of which about one half is for childhood exacerbations. Exacerbations are relatively infrequent and short-lived but their importance to patients is emphasised in the Global Initiative for Asthma whose major goals include “to prevent asthma exacerbations”. Everyone breathes out a gas called nitric oxide. Exhaled nitric oxide can be measured using a special breathing device. People with asthma breathe out more nitric oxide than people without asthma because nitric oxide is produced by the allergic cells which are present in the lungs of people with asthma. These allergic cells build up before an asthma attack. The aim of this study is to find out whether measuring fractional exhaled nitric oxide (FeNO) can guide asthma treatment and help prevent asthma attacks.
Who can participate?
Children aged between 6 and 16 who have been diagnosed with asthma and are currently being treated with inhaled steroids and who have had an asthma attack treated with steroid tablets.
What does the study involve?
Participants are randomly allocated to one of two groups. Those in the first group have their asthma treatment guided by symptoms and breath tests to measure FeNO. Those in the second group are treated according to the symptoms they are having alone. Participants in both groups are followed up after three, six, nine and twelve months in order to find out how many asthma exacerbations they have had and assessments of their quality of life. Participants are also offered additional allergy testing, which involves a blood test and a coughing up spit test. Additionally around 20 children are invited to take part in an interview at the end of the twelve month follow-up to explore attitudes to, and acceptability of the FeNO measurements. Five research nurses are also interviewed about the practicality of FeNO measurements.
What are the possible benefits and risks of participating?
All children will benefit from regular asthma assessments as part of the study. Asthma treatment is currently only guided by symptoms, and so children in the group where asthma treatment is guided by symptoms will continue to get current best asthma treatment. There is a risk that the optional allergy testing will cause itchiness on the participant’s arm for a short time. The optional coughing up spit test may make the participant cough and possibly also wheeze, but this will only be conducted following a lung function check.
Where is the study run from?
25 hospitals around the UK
When is the study starting and how long is it expected to run for?
February 2017 to January 2021
Who is funding the study?
National Institute for Health Research (UK)
Who is the main contact?
1. Dr Stephen Turner (scientific)
s.w.turner@abdn.ac.uk
2. Mrs Jess Wood (public)
raaceno@abdn.ac.uk
Contact information
Scientific
Child Health
Royal Aberdeen Children’s Hospital
Aberdeen
AB25 2ZG
United Kingdom
 ORCID ID |
0000-0001-8393-5060 |
|---|---|
| Phone | +44 1224 438470 |
| s.w.turner@abdn.ac.uk |
Public
Centre for Healthcare Randomised Trials (CHaRT)
Health Services Research Unit
University of Aberdeen
Health Sciences Building
Foresterhill
Aberdeen
AB51 2ZD
United Kingdom
| Phone | +44 1224 438179 |
|---|---|
| raaceno@abdn.ac.uk |
Study information
| Study design | Randomized; Both; Design type: Screening, Diagnosis, Device, Active Monitoring, Qualitative |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| Scientific title | Reducing Asthma Attacks in Children using Exhaled Nitric Oxide as a biomarker to inform treatment strategy - a randomised trial (RAACENO) |
| Study acronym | RAACENO |
| Study hypothesis | Current study hypothesis as of 08/02/2021: Study aim: The aim of the study is to compare treatment guided by exhaled nitric oxide and symptoms against treatment guided by symptoms alone (standard care), in children with asthma who are at risk of an asthma attack (ie have had an asthma attack in the previous 12 months), in terms of the presence of any asthma exacerbations over 12 months requiring prescription of OCS. Hypothesis: The proportion of children with ≥1 asthma exacerbation will be reduced when asthma treatment guided by FeNO plus symptoms is compared to treatment guided only by symptoms. _____ Previous study hypothesis: Study aim: The aim of the study is to compare treatment guided by exhaled nitric oxide and symptoms against treatment guided by symptoms alone (standard care), in children with asthma who are at risk of an asthma attack (ie have had an asthma attack in the previous 12 months), in terms of the presence of any asthma exacerbations over 12 months requiring prescription of OCS for 3-7 consecutive days. Hypothesis: The proportion of children with ≥1 asthma exacerbation will be reduced when asthma treatment guided by FeNO plus symptoms is compared to treatment guided only by symptoms. |
| Ethics approval(s) | North of Scotland Research Ethics Committee 1, 17/10/2016, ref: 16/NS/0106 |
| Condition | Asthma |
| Intervention | Eligible and consenting participants will be randomised to one of the two groups (treatment decisions based on FeNO plus symptoms [interventional arm] or treatment decisions based on symptoms alone [standard care]) using a 24-hour telephone Interactive Voice Response randomisation application or via a web-based application, both hosted by CHaRT. Random allocation will use a minimisation algorithm (stratification by centre, age (<11 years, ≥11 years) sex and asthma severity as evidenced by BTS/SIGN treatment step (BTS step 2, BTS step 3, BTS step 4) including a random element (20%). Experimental arm: Asthma treatment decisions will be guided by Fractional Exhaled Nitric Oxide (FeNO) and symptoms. The experimental intervention and subsequent adjustment of treatment steps are applied at recruitment, and at each of the follow-up visits (3, 6, 9 and 12 months). FeNO guides treatment to either early escalation of anti-inflammatory medication (algorithm 1, elevated FeNO) or early intervention with bronchodilators (algorithm 2, FeNO not elevated). Control arm: Asthma treatment decisions will be guided by symptoms alone. The control intervention and subsequent adjustment of treatment steps are applied at recruitment, and at each of the follow-up visits (3, 6, 9 and 12 months). Although FeNO will be measured in children in this arm at recruitment and at each of the follow-up visits, the results of the FeNO will not be used in treatment decisions for this arm of the trial. The FeNO will be used as outcome data only. For participants in this group, the FeNO result will not be available to the patient’s GP or paediatrician (where appropriate) during the trial period. In both arms, treatment decisions will be protocolised through the study website. Data required for step up/down decisions are entered into the study website which contains the algorithm for step up/down treatment decisions; this removes subjectivity from the treatment decisions. The trial algorithm applies to participants in both arms of the trial up to 12 month assessment. |
| Intervention type | Other |
| Primary outcome measure | Current primary outcome measure as of 08/02/2021: Asthma exacerbation (attack) requiring prescription (and/or use of) one or more course of OCS in the 12 months after randomisation (yes/no). Outcomes will be assessed at the 3, 6, 9 and 12 months follow-up visits. In protocol version 3 (31 August 2017) we refined the definition of the primary outcome to reflect a change in treatment, where some exacerbations were being treated with a single dose of oral corticosteroid; and clarified that the primary source of information on exacerbations would be the child and parent or carer; with GP records used only where this information was missing. _____ Previous primary outcome measure: Asthma exacerbation (attack) requiring prescription of OCS for 3-7 consecutive days determined from a patient held diary and verified by GP records where possible in the 12 months after randomisation (yes/no). Outcomes will be assessed at the 3, 6, 9 and 12 months follow-up visits. |
| Secondary outcome measures | 1. Time to first exacerbation is determined from the child/parent or carer and from GP records in the 12 months after randomisation. Outcomes will be assessed at 3, 6, 9 and 12 months post randomisation 2. Number of exacerbations during follow up, based on prescribed oral corticosteroid, is assessed by responses to asthma attacks that have required oral steroid tablets on the follow-up CRF at 3,6,9, and 12 months follow-up determined from the child/parent or carer and from GP records in the 12 months after randomisation 3. Need for unscheduled healthcare assessment during follow up (yes/no) is measured by responses to health service use on the follow-up CRF at 3,6,9 and 12 months follow-up determined from the child/parent or carer and from GP records in the 12 months after randomisation 4. Number of unscheduled health assessments is measured by responses on the follow-up CRF to health service use at 3,6,9 and 12 months follow-up determined from the child/parent or carer and from GP records in the 12 months after randomisation 5. Asthma control during follow up (i.e. age-appropriate Asthma Control Test score) is assessed by responses to the Asthma Control Test (ACT)/Children’s Asthma Control Test (CACT) - questionnaires completed by child/parent or carer at baseline, and at 3, 6, 9 and 12 month follow-up appointments 6. Asthma severity (%FEV1) is measured using spirometry at baseline and at 3, 6, 9 and 12 month follow-up appointments. 7. Fractional exhaled nitric oxide (FeNO) is measured by Niox Vero device at baseline, and 3, 6, 9 and 12 month follow-up appointments 8. Dose of ICS during the 12 months follow up (i.e. daily dose of budesonide equivalent averaged over 3 months) is assessed from current asthma treatment and from adherence to treatment (measured using adherence monitors); this data is collected at 3, 6, 9 and 12 months follow-up 9. Health status is assessed using the Paediatric Asthma Quality of Life Questionnaire (PAQLQ); a questionnaire completed by the child/parent or carer at baseline and 12 months 10. Exploration of experiences and ascertainment of acceptability of the intervention will be collected through participant interviews following 12 month follow-up 11. Health economic evaluation is undertaken using from GP records and participant reported data at baseline, 3, 6, 9 and 12 months follow-up |
| Overall study start date | 01/02/2017 |
| Overall study end date | 31/01/2021 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Child |
| Lower age limit | 6 Years |
| Upper age limit | 15 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 502; UK Sample Size: 502 |
| Total final enrolment | 515 |
| Participant inclusion criteria | 1. Asthma diagnosed or confirmed by consultant paediatrician (or Read code for asthma if recruited in primary care) 2. Aged 6 years or older and not yet reached the date of their 16th birthday 3. Currently prescribed inhaled corticosteroids (<1000mcg budesonide equivalent per day in those <12 years; <2000 mcg budesonide equivalent per day for older children) 4. At least one patient/parent reported-asthma exacerbation treated with oral corticosteroids in the 12 months prior to recruitment |
| Participant exclusion criteria | 1. Unable to provide FeNO measurement at baseline assessment (expected prevalence <5%) 2. Other chronic respiratory conditions which also have exacerbations 3. Current treatment with maintenance oral steroids |
| Recruitment start date | 01/06/2017 |
| Recruitment end date | 01/08/2019 |
Locations
Countries of recruitment
- England
- Scotland
- United Kingdom
Study participating centres
Aberdeen
AB25 2ZG
United Kingdom
Birmingham
B4 6NH
United Kingdom
Duckworth Lane
Bradford
BD9 6RJ
United Kingdom
Brighton
BN2 5BE
United Kingdom
Upper Maudlin Street
Bristol
BS2 8BJ
United Kingdom
Uttoxeter Road
Derby
DE22 3NE
United Kingdom
Royal Hospital for Sick Children
9 Sciennes Road
Edinburgh
EH9 1LF
United Kingdom
1345 Govan Road
Glasgow
G51 4TF
United Kingdom
Chelsea
London
SW3 6NP
United Kingdom
Crosshouse
Kilmarnock
KA2 0BE
United Kingdom
Infirmary Square
Leicester
LE1 5WW
United Kingdom
Liverpool
L14 5AB
United Kingdom
Manchester
M13 9WL
United Kingdom
Royal Victoria Infirmary
Newcastle upon Tyne
NE1 4LP
United Kingdom
Derby Road
Nottingham
NG7 2UH
United Kingdom
Tremona Road
Southampton
SO16 6YD
United Kingdom
Newcastle Road
Stoke-on-Trent
ST4 6PQ
United Kingdom
Heath Town
Wolverhampton
WV10 0QP
United Kingdom
Dundee
DD1 9SY
United Kingdom
Barnsley
S75 2EP
United Kingdom
Sheffield
S10 2TH
United Kingdom
Exeter
EX2 5DW
United Kingdom
Plymouth
PL6 8DH
United Kingdom
Walsall
WS2 9PS
United Kingdom
Leeds
LS1 3EX
United Kingdom
London
SE5 9RS
United Kingdom
Whitechapel Road
Whitechapel
London
E1 1FR
United Kingdom
Manchester
M23 9LT
United Kingdom
London
SW17 0QT
United Kingdom
Shrewsbury
SY3 8XQ
United Kingdom
Chester
CH2 1UL
United Kingdom
Harrogate
HG2 7SX
United Kingdom
Dudley
DY1 2HQ
United Kingdom
Wishaw
ML2 0DP
United Kingdom
Oldham
OL1 2JH
United Kingdom
Preston
PR2 9HT
United Kingdom
Ormskirk
L39 2AZ
United Kingdom
Upton
Wirral
CH49 5PE
United Kingdom
Hertford
SG14 1JA
United Kingdom
Haymeands Lane
Bishops Stortford
CM23 5JH
United Kingdom
Ipswich
IP1 3NQ
United Kingdom
Costessey
NR5 0GB
United Kingdom
Bury St Edmunds
IP31 2HD
United Kingdom
Norwich
NR1 3JJ
United Kingdom
Norwich
NR3 1SE
United Kingdom
Sponsor information
University/education
Foresterhill House Annex
Foresterhill
Aberdeen
AB25 2ZB
Scotland
United Kingdom
| Phone | +44 1224 551123 |
|---|---|
| researchgovernance@abdn.ac.uk | |
"ROR" |
https://ror.org/00ma0mg56 |
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 | 31/01/2022 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | A final report of the study findings will be presented to the funder at the end of the study. It is also envisaged that the main results of the trial will be published in a peer-reviewed medical/scientific journal under an open-access agreement. Once the main report has been published, a lay summary of the findings will be sent in a final RAACENO Newsletter to all those who participated in the trial. |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are/will be available upon request from Dr Steve Turner (s.w.turner@abdn.ac.uk) |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | protocol | 04/10/2019 | 07/10/2019 | Yes | No |
| Results article | 28/01/2022 | 02/02/2022 | Yes | No | |
| Other publications | Qualitative process evaluation | 05/01/2023 | 07/06/2023 | Yes | No |
| Results article | 01/05/2022 | 07/06/2023 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No | ||
| Other publications | Cost analysis | 27/05/2024 | 28/05/2024 | Yes | No |
Editorial Notes
28/05/2024: Publication reference added.
07/06/2023: Publication references added.
02/02/2022: Publication reference added.
10/02/2021: The following trial participating centres were added: Tayside Children’s Hospital, Barnsley Hospital, Sheffield Children’s Hospital, Royal Devon & Exeter Hospital, Derriford Hospital, Walsall Manor Hospital, Leeds General Infirmary, King's College Hospital, Barts Health NHS Trust, Wythenshawe Hospital, St George Hospital, Royal Shrewsbury Hospital, Countess of Chester Hospital, Harrogate District Hospital, Russells Hall Hospital, Wishaw General Hospital, Royal Oldham Hospital, Royal Preston Hospital, Ormskirk District General Hospital, Arrowe Park Hospital, Hanscombe House Surgery, Parsonage Surgery, Barrack Lane Medical Centre, Roundwell Medical Centre, Ixworth Surgery, Lakenham Surgery, Castle Partnership.
08/02/2021: The following changes were made to the trial record:
1. The study hypothesis was changed.
2. The primary outcome measure was changed.
07/10/2019: Publication reference added.
12/09/2019: The recruitment end date was changed from 08/08/2019 to 01/08/2019.
04/09/2019: The following changes were made to the trial record:
1. The recruitment end date was changed from 01/08/2019 to 08/08/2019.
2. The total final enrolment was added.
03/07/2019: The recruitment end date was changed from 01/06/2019 to 01/08/2019.
26/03/2019: The condition has been changed from "Specialty: Children, Primary sub-specialty: Respiratory and Cystic Fibrosis; UKCRC code/ Disease: Respiratory/ Other diseases of the respiratory system" to "Asthma" following a request from the NIHR.
13/04/2017: Verified study information with principal investigator.
