Plain English Summary
Background and study aims
Wheezing is a whistling sound caused by breathing through narrowed airways. It is a common problem in young children. Many preschool children have repeated wheezy episodes, and share characteristics with older children who have asthma. Like them, they are often treated with inhaled salbutamol. However, in the preschool years it is difficult to make a definite diagnosis of asthma, and there is much less consensus about treatment. The correct dose of inhaled salbutamol has been determined in adults and older children by studying their response to a range of doses. This has not been possible in children below 7 years of age who are unable to cooperate with the tests. Doctors commonly ask parents to use any dose between 200 to 1000 micrograms of salbutamol to help their child's wheezy spells. Recently, however, a lung function test that could be used for this purpose has been validated in young children. This study proposes to use this test (Rint) to find the correct dose range that produces an adequate response in most young children. Recent work also suggests that even large doses of salbutamol may not be effective in relieving symptoms in some children. We will define the extent of this problem, as there are alternative 'relievers' that could then be used to help these children. We will also explore whether a simple genetic test that could predict this lack of response.
Who can participate?
Children aged 2 years 6 months to 6 years 11 months, with recurrent wheeze (at least 3 episodes of wheezing over the previous 12 months)
What does the study involve?
Participants are randomly allocated to inhale one of four different doses of salbutamol. Lung function is tested before and 20 minutes after inhaling salbutamol. Saliva and urine samples are also collected. The one-off study visit lasts for around two and half hours and there is no follow up.
What are the possible benefits and risks of participating?
Involvement in the study and the resulting discussions may provide the parent/carer and child with a greater understanding of the processes causing wheeze. This study does not have any risk of physical or psychological harm, and there are no painful procedures. Some young children are bothered by the clicking sounds during the breathing test, so we spend a little time beforehand getting them used to the equipment. The researchers work with the parents to distract them during the measurements. The collection of the urine and saliva samples does not involve any risks to the child. Travel expenses to the hospital (up to £20) for the research study visit can be reimbursed.
Where is the study run from?
Royal Sussex County Hospital (UK)
When is the study starting and how long is it expected to run for?
January 2014 to June 2017
Who is funding the study?
National Institute for Health Research (UK)
Who is the main contact?
Dr Akshat Kapur, akshat.kapur@nhs.net
Study website
Contact information
Type
Scientific
Contact name
Prof Somnath Mukhopadhyay
ORCID ID
Contact details
Academic Department of Paediatrics
Royal Alexandra Children's Hospital
Level 6
Room 601
Eastern Road
Brighton
BN2 5BE
United Kingdom
+44 (0)1273 696955 x62409
S.Mukhopadhyay@bsms.ac.uk
Type
Public
Contact name
Dr Akshat Kapur
ORCID ID
Contact details
University Hospitals Sussex NHS Foundation Trust
Kemptown
Brighton
BN2 1DH
United Kingdom
+44 (0)1273 641469
akshat.kapur@nhs.net
Type
Scientific
Contact name
Prof Somnath Mukhopadhyay
ORCID ID
Contact details
Academic Department of Paediatrics
Royal Alexandra Children's Hospital
Level 6
Room 601
Eastern Road
Brighton
BN2 5BE
United Kingdom
+44 (0)1273 696955 (x62397)
somnath.mukhopadhyay@nhs.net
Additional identifiers
EudraCT/CTIS number
2014-001978-33
IRAS number
ClinicalTrials.gov number
Protocol/serial number
16931
Study information
Scientific title
How can we optimise inhaled beta2 agonist dose as 'reliever' medicine for wheezy preschool children?
Acronym
OpSal
Study hypothesis
The study will help develop the evidence for the correct dose of salbutamol in younger children with recurrent wheeze who have been prescribed salbutamol by their doctor. It is possible that a small dose of salbutamol, such as 2 puffs (200 μg) is adequate for most of these children. If this is the case, larger doses such as 1000 μg, should not be prescribed (as is current practice) as they may be inducing side-effects in these children. Secondly, some younger children who currently prescribed larger doses of salbutamol may in fact be 'poor‘ or 'non-responders' to salbutamol due to their genetic constitution. Such children may benefit from alternative 'reliever' medicines, such as ipratropium or montelukast. We intend to investigate whether an effective marker can be identified for poor salbutamol efficacy in these younger children.
Ethics approval(s)
East of Scotland Research Ethics Service REC 2 , 21/07/2014, ref: 14/ES/0072
Study design
Randomised; Interventional; Design type: Treatment
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Study setting(s)
Hospital
Study type
Treatment
Patient information sheet
Not available in web format, please use contact details to request a patient information sheet
Condition
Topic: Children; Subtopic: All Diagnoses; Disease: All Diseases
Intervention
1. Collection of DNA sample using non-invasive Oragene DNA Collection kits
2. Collection of urine sample after each of the two doses of salbutamol will be attempted
3. Data Collection
4. Rint Measurements: At baseline and 20 minutes after each of the two doses of salbutamol
5. Salbutamol Doses: No control group. Participants are randomised to 1 of 4 dosage schedules:
5.1. 100 μg Salbutamol →+300 μg = 400 μg Salbutamol
5.2. 100 μg Salbutamol →+500 μg = 600 μg Salbutamol
5.3. 200 μg Salbutamol →+600 μg = 800 μg Salbutamol
5.4. 200 μg Salbutamol →+200 μg = 400 μg Salbutamol
The one off study visit lasts for around two and half hours. No follow up.
Intervention type
Drug
Pharmaceutical study type(s)
Phase
Not Applicable
Drug/device/biological/vaccine name(s)
Salbutamol
Primary outcome measure
Bronchodilator response to salbutamol using lung function test (interrupter resistance Rint) at baseline and 30 minutes after each dose of salbutamol.
Secondary outcome measures
N/A
Overall study start date
01/01/2014
Overall study end date
30/06/2019
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Age 2 years 6 months to 6 years 11 months
2. Recurrent wheeze, defined as at least 3 episodes of wheeze over the previous 12 months by the parent
Participant type(s)
Patient
Age group
Child
Lower age limit
2 Years
Upper age limit
6 Years
Sex
Both
Target number of participants
Planned Sample Size: 155; UK Sample Size: 155
Total final enrolment
84
Participant exclusion criteria
1. Other major airway or lung disease, e.g. chronic lung disease of prematurity, cystic fibrosis, and abnormal airway anatomy
2. Recent (within 2 weeks) treatment with systemic corticosteroids or leukotriene inhibitors
3. Participants involved in other research currently or recently
Recruitment start date
15/12/2014
Recruitment end date
30/06/2017
Locations
Countries of recruitment
England, United Kingdom
Study participating centre
Royal Sussex County Hospital
Clinical Investigation and Research Unit, Eastern Road
Brighton
BN2 5BE
United Kingdom
Funders
Funder type
Government
Funder name
National Institute for Health Research
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
Funding Body Type
government organisation
Funding Body Subtype
National government
Location
United Kingdom
Results and Publications
Publication and dissemination plan
A research summary will be provided to participants if they request to be made aware of this. Trial results will be communicated to healthcare professionals, the public and other relevant groups at conferences, press releases, through published papers and via parent groups. The full protocol will be published on the online journal www.trialsjournal.com.
Intention to publish date
31/12/2022
Individual participant data (IPD) sharing plan
IPD sharing plan summary
Not expected to be made available
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | protocol | 11/11/2016 | Yes | No | |
| Basic results | 09/06/2021 | No | No | ||
| Basic results | 09/06/2021 | 19/07/2021 | No | No | |
| HRA research summary | 28/06/2023 | No | No |
Additional files
- ISRCTN15513131_BasicResults.pdf Uploaded 09/06/2021
- ISRCTN15513131_BasicResults.pdf