Condition category
Respiratory
Date applied
10/04/2017
Date assigned
12/04/2017
Last edited
13/04/2017
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

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

Trial website

https://www.raaceno.co.uk

Contact information

Type

Scientific

Primary contact

Dr Stephen Turner

ORCID ID

http://orcid.org/0000-0001-8393-5060

Contact details

Child Health
Royal Aberdeen Children’s Hospital
Aberdeen
AB25 2ZG
United Kingdom
+44 1224 438470
s.w.turner@abdn.ac.uk

Type

Public

Additional contact

Mrs Jess Wood

ORCID ID

Contact details

Centre for Healthcare Randomised Trials (CHaRT)
Health Services Research Unit
University of Aberdeen
Health Sciences Building
Foresterhill
Aberdeen
AB51 2ZD
United Kingdom
+44 1224 438179
raaceno@abdn.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

34390

Study information

Scientific title

Reducing Asthma Attacks in Children using Exhaled Nitric Oxide as a biomarker to inform treatment strategy - a randomised trial (RAACENO)

Acronym

RAACENO

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

North of Scotland Research Ethics Committee 1, 17/10/2016, ref: 16/NS/0106

Study design

Randomised; Both; Design type: Screening, Diagnosis, Device, Active Monitoring, Qualitative

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Specialty: Children, Primary sub-specialty: Respiratory and Cystic Fibrosis; UKCRC code/ Disease: Respiratory/ Other diseases of the respiratory system

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

Phase

Drug names

Primary outcome measures

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 trial start date

01/02/2017

Overall trial end date

31/01/2021

Reason abandoned

Eligibility

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 type

Patient

Age group

Child

Gender

Both

Target number of participants

Planned Sample Size: 502; UK Sample Size: 502

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

01/06/2019

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Royal Aberdeen Children's Hospital
Westburn Road
Aberdeen
AB25 2ZG
United Kingdom

Trial participating centre

Birmingham Children's Hospital
Steelhouse Lane
Birmingham
B4 6NH
United Kingdom

Trial participating centre

Bradford Teaching Hospitals NHS Foundation Trust
Children's Services Directorate Duckworth Lane
Bradford
BD9 6RJ
United Kingdom

Trial participating centre

Royal Alexandra Children’s Hospital
Eastern Road
Brighton
BN2 5BE
United Kingdom

Trial participating centre

Bristol Royal Hospital for Children
Paul O'Gorman Building Upper Maudlin Street
Bristol
BS2 8BJ
United Kingdom

Trial participating centre

Derbyshire Children’s Hospital
Royal Derby Hospital Uttoxeter Road
Derby
DE22 3NE
United Kingdom

Trial participating centre

Royal Hospital for Sick Children
NHS Lothian Royal Hospital for Sick Children 9 Sciennes Road
Edinburgh
EH9 1LF
United Kingdom

Trial participating centre

Royal Hospital for Children
NHS Greater Glasgow & Clyde 1345 Govan Road
Glasgow
G51 4TF
United Kingdom

Trial participating centre

Royal Brompton Hospital
Sydney Street Chelsea
London
SW3 6NP
United Kingdom

Trial participating centre

University Hospital Crosshouse
Kilmarnock Road Crosshouse
Kilmarnock
KA2 0BE
United Kingdom

Trial participating centre

Leicester Children's Hospital
Leicester Royal Infirmary Infirmary Square
Leicester
LE1 5WW
United Kingdom

Trial participating centre

Alder Hey Children's Hospital
E Prescot Road
Liverpool
L14 5AB
United Kingdom

Trial participating centre

Manchester Royal Infirmary
Oxford Road
Manchester
M13 9WL
United Kingdom

Trial participating centre

Great North Children's Hospital
Victoria Wing Royal Victoria Infirmary
Newcastle upon Tyne
NE1 4LP
United Kingdom

Trial participating centre

Nottingham Children's Hospital
Queen's Medical Centre Derby Road
Nottingham
NG7 2UH
United Kingdom

Trial participating centre

Southampton Children's Hospital
Southampton General Hospital Tremona Road
Southampton
SO16 6YD
United Kingdom

Trial participating centre

Royal Stoke Children's Service
Royal Stoke University Hospital Newcastle Road
Stoke-on-Trent
ST4 6PQ
United Kingdom

Trial participating centre

New Cross Hospital
Wolverhampton Road Heath Town
Wolverhampton
WV10 0QP
United Kingdom

Sponsor information

Organisation

University of Aberdeen and NHS Grampian

Sponsor details

Foresterhill House Annex
Foresterhill
Aberdeen
AB25 2ZB
United Kingdom
+44 1224 551123
researchgovernance@abdn.ac.uk

Sponsor type

University/education

Website

Funders

Funder type

Government

Funder name

National Institute for Health Research

Alternative name(s)

NIHR

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

United Kingdom

Results and Publications

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)

Intention to publish date

31/01/2022

Participant level data

Available on request

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

13/04/2017: Verified study information with principal investigator.