WheezingPhase 4KIWINCT04584034
Bronchodilators for Wheeze in Young Children Presenting to Primary Care: a Randomised, Placebo-controlled, Multicentre, Parallel Group Trial
A Phase 4 study testing Salbutamol in people with Wheezing, run by UMC Utrecht.
Trial summary
Ten percent of infants are prescribed short-acting bronchodilators (i.e. salbutamol) for wheezing every year, yet evidence to support this treatment in children younger than two years old is scarce. Read more about this study
- Who is it for?
- Ages 6 to 24 months
- Conditions the study is for
- Wheezing
- What is being tested?
- Salbutamol
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Sep 2021to Apr 2023
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 24 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Presenting to their primary care physician because of wheezing as confirmed by clinical examination (chest auscultation)
- A baseline score of 7 or higher on a parent-reported respiratory symptom score
Who cannot join
- Prematurity (<37 weeks)
- Major congenital malformations
- Pre-existing pulmonary disease as diagnosed by a paediatrician
- Continuous use of inhalation medication
- Physician visit because of wheezing in previous two weeks
- Use of inhalation medication in the previous two weeks
- Wheezing as a result of upper airway obstruction (i.e. laryngitis subglottica/pseudocroup)
- Severe illness requiring inhalation medication, prescription of antibiotics, or hospital referral during the consultation of inclusion
About this study
Ten percent of infants are prescribed short-acting bronchodilators (i.e. salbutamol) for wheezing every year, yet evidence to support this treatment in children younger than two years old is scarce. The aim of this study is to evaluate the effectiveness and safety of salbutamol for treatment of wheezing in young children who present to their primary care physician.
In this study, the investigators will compare the effect of a 7-day treatment with salbutamol to the effect of 7-day treatment with a placebo. The main effect will be measured by evaluating a parent-reported symptom score. Additionally, the investigators will look at the presence of wheeze after 5 days, time to recovery, adverse events, healthcare utilisation, medication prescriptions, cost-effectiveness, and parent satisfaction with treatment.
Read the detailed description
BACKGROUND: Worldwide, 30% of all infants and young children experience an episode of wheezing (Matricaldi et al. 2008; Mallol at al. 2010; Martinez et al. 1995). Currently, there is no evidence to underpin the management of these children. National Belgian and Dutch primary care professional guidelines propose 'a trial of treatment' with short acting bronchodilators (i.e. salbutamol) for wheezing children below the age of six years and to evaluate treatment effect after 1 to 2 weeks, but convincing evidence is lacking (Chavasse et al. 2002).
The effect of salbutamol has been studied well in children with proven asthma and is considered the first-line treatment in all patients in international asthma guidelines. However, trial findings of children with asthma are not applicable to primary care infants and young children with acute wheeze for several reasons; the anatomy and physiology in younger children differs significantly from those in older children and many infants and young children with an acute episode of wheezing do not experience further wheezing episodes later in life. As a result, it is at present unclear whether salbutamol inhalation therapy confers any benefit in young children who wheeze.
OBJECTIVE: To evaluate the (cost-)effectiveness of salbutamol inhalations (4x200μg for 7 days) versus placebo in children aged 6-24 months presenting to their primary care physician with wheezing.
DESIGN: A primary care based, randomised, placebo-controlled, multicentre, parallel group trial in 40 general practices and community paediatric practices in Belgium and the Netherlands.
- Conditions
- Wheezing
- Being tested
- Salbutamol, Placebo
- Keywords
- Wheeze, Viral respiratory illnesses, Pre-school age children, Primary care, General practice, Salbutamol, Bronchodilators, Therapeutic trial
- Medical subject headings
- Respiratory Sounds
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SalbutamolDrug
Also called Ventolin, β2-adrenoceptor agonist, Bronchodilator, Salbutamol sulfate
Salbutamol will be delivered using a Babyhaler spacer device. Ventolin will be used, brandname for Salbutamol sulfate. Ventolin contains the propellant HFA 134a.
PlaceboDrug
Also called Mock inhaler
The placebo will be delivered using a Babyhaler spacer device. The placebo will contain only the propellant HFA 134a.
| Study group | Role | What they receive |
|---|---|---|
| Salbutamol | Active comparator | Salbutamol inhalation 4x200ug daily for 7 days, delivered using a Babyhaler Receives: Drug: Salbutamol |
| Placebo | Placebo comparator | Placebo 4 x 2 inhalations daily for 7 days, delivered using a Babyhaler Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Course of the parent reported respiratory symptom score
Scores on an arbitrary ordinal scale of 0 to 3 (0= no symptoms, 1= a bit (mild), 2= quite bad (moderate), 3= very bad (severe)) are recorded by parents for wheeze, cough and difficulty in breathing for both day and night, giving a maximum possible symptom score of 18 for each day.
Measured: 5 days
Secondary outcomes (8)
Time to recovery
Recovery defined as a respiratory symptom score of 5 or lower indicating only trivial symptoms
Measured: 28 days
Adverse effects
Measured: 7 days
Health care resource use
Primary care physician re-consultations, medication prescriptions (e.g. antibiotics), specialist consultations and hospital admissions
Measured: 28 days
Persistent wheezing on auscultation on day 5
To maximise objectivity, lung sounds will be recorded (digital stethoscope) and evaluated by an expert panel at a later date
Measured: on day 5
Day of parent reported recovery
The number of the day on which parents felt their child was recovered
Measured: 28 days
Parent satisfaction with care
Single direct question "How satisfied are you with the treatment with study medication on a scale from 1 to 4 (very satisfied, satisfied, unsatisfied, very unsatisfied)?
Measured: on day 28
Out-of-pocket expenses
Parent reported expenses for over-the-counter medication, additional travel, parking and child care, recorded in the study diary
Measured: 14 days
Parent productivity losses
Assessed using the iMTA Productivity Cost questionnaire (iPCQ)
Measured: 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Oct 2020
- Study startSep 2021 (estimated)
- Primary completionApr 2023 (estimated)
- Study completionApr 2023 (estimated)
Why it stopped: Premature ending of the study due to impossibility of obtaining a suitable placebo-inhaler
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for WheezingStudies of the same condition, open and under way.
- More trials run by UMC UtrechtThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Individually randomised, placebo-controlled, multicentre, parallel group trial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- UMC Utrecht
- Sponsor type
- University, hospital or other
- Collaborators
- KU Leuven, Maastricht University Medical Center, Universiteit Antwerpen, Université de Liège
- Responsible party
- Principal investigator, prof. dr. R.A.M.J. Damoiseaux, UMC Utrecht
- Investigators
- Roger AMJ Damoiseaux, Professor, Principal investigator, Julius Center, UMC UtrechtAnn van den Bruel, Professor, Principal investigator, KU Leuven
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04584034
- Sponsor's protocol ID
- NL72651
- Acronym
- KIWI
- Status last verified
- Jul 2021
- First submitted
- 3 Sep 2020
- Last updated
- 23 Jul 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: We will make our data accessable for verification and future research (other researchers / spin-off projects), yet these will be shared under restrictions. Data cannot be reused without consulting the research team.
Publications
Matricardi PM, Illi S, Gruber C, Keil T, Nickel R, Wahn U, Lau S. Wheezing in childhood: incidence, longitudinal patterns and factors predicting persistence. Eur Respir J. 2008 Sep;32(3):585-92. doi: 10.1183/09031936.00066307. Epub 2008 May 14.
PubMed 18480107Martinez FD, Wright AL, Taussig LM, Holberg CJ, Halonen M, Morgan WJ. Asthma and wheezing in the first six years of life. The Group Health Medical Associates. N Engl J Med. 1995 Jan 19;332(3):133-8. doi: 10.1056/NEJM199501193320301.
PubMed 7800004Mallol J, Garcia-Marcos L, Sole D, Brand P; EISL Study Group. International prevalence of recurrent wheezing during the first year of life: variability, treatment patterns and use of health resources. Thorax. 2010 Nov;65(11):1004-9. doi: 10.1136/thx.2009.115188. Epub 2010 Sep 20.
PubMed 20855440Chavasse R, Seddon P, Bara A, McKean M. Short acting beta agonists for recurrent wheeze in children under 2 years of age. Cochrane Database Syst Rev. 2002;2002(3):CD002873. doi: 10.1002/14651858.CD002873.
PubMed 12137663
Study at a glance
From the registry record, last updated by the sponsor on 23 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Bronchodilators for Wheeze in Young Children Presenting to Primary Care: a Randomised, Placebo-controlled, Multicentre, Parallel Group Trial
- ClinicalTrials.gov ID
- NCT04584034
- Acronym / sponsor ID
- KIWI / NL72651
- Conditions
- Wheezing
- Keywords
- Wheeze, Viral respiratory illnesses, Pre-school age children, Primary care, General practice, Salbutamol, Bronchodilators, Therapeutic trial
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Premature ending of the study due to impossibility of obtaining a suitable placebo-inhaler
- Enrolment
- 0 participants (actual)
- Lead sponsor
- UMC UtrechtUniversity, hospital or other
- Collaborators
- KU Leuven, Maastricht University Medical Center, Universiteit Antwerpen, Université de Liège
- Study start
- Sep 2021 (estimated)
- Primary completion
- Apr 2023 (estimated)
- Study completion
- Apr 2023 (estimated)
- First posted
- 12 Oct 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Ten percent of infants are prescribed short-acting bronchodilators (i.e. salbutamol) for wheezing every year, yet evidence to support this treatment in children younger than two years old is scarce. The aim of this study is to evaluate the effectiveness and safety of salbutamol for treatment of wheezing in young children who present to their primary care physician.
In this study, the investigators will compare the effect of a 7-day treatment with salbutamol to the effect of 7-day treatment with a placebo. The main effect will be measured by evaluating a parent-reported symptom score. Additionally, the investigators will look at the presence of wheeze after 5 days, time to recovery, adverse events, healthcare utilisation, medication prescriptions, cost-effectiveness, and parent satisfaction with treatment.
Detailed description
BACKGROUND: Worldwide, 30% of all infants and young children experience an episode of wheezing (Matricaldi et al. 2008; Mallol at al. 2010; Martinez et al. 1995). Currently, there is no evidence to underpin the management of these children. National Belgian and Dutch primary care professional guidelines propose 'a trial of treatment' with short acting bronchodilators (i.e. salbutamol) for wheezing children below the age of six years and to evaluate treatment effect after 1 to 2 weeks, but convincing evidence is lacking (Chavasse et al. 2002).
The effect of salbutamol has been studied well in children with proven asthma and is considered the first-line treatment in all patients in international asthma guidelines. However, trial findings of children with asthma are not applicable to primary care infants and young children with acute wheeze for several reasons; the anatomy and physiology in younger children differs significantly from those in older children and many infants and young children with an acute episode of wheezing do not experience further wheezing episodes later in life. As a result, it is at present unclear whether salbutamol inhalation therapy confers any benefit in young children who wheeze.
OBJECTIVE: To evaluate the (cost-)effectiveness of salbutamol inhalations (4x200μg for 7 days) versus placebo in children aged 6-24 months presenting to their primary care physician with wheezing.
DESIGN: A primary care based, randomised, placebo-controlled, multicentre, parallel group trial in 40 general practices and community paediatric practices in Belgium and the Netherlands.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Individually randomised, placebo-controlled, multicentre, parallel group trial
| Arm | Type | Receives |
|---|---|---|
| Salbutamol | Active comparator | Drug: SalbutamolSalbutamol inhalation 4x200ug daily for 7 days, delivered using a Babyhaler |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo 4 x 2 inhalations daily for 7 days, delivered using a Babyhaler |
Who may qualify
- Ages
- 6 to 24 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (2 listed)
- Presenting to their primary care physician because of wheezing as confirmed by clinical examination (chest auscultation)
- A baseline score of 7 or higher on a parent-reported respiratory symptom score
Key exclusion criteria (8 listed)
- Prematurity (<37 weeks)
- Major congenital malformations
- Pre-existing pulmonary disease as diagnosed by a paediatrician
- Continuous use of inhalation medication
- Physician visit because of wheezing in previous two weeks
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SalbutamolAlso: Ventolin, β2-adrenoceptor agonist, Bronchodilator, Salbutamol sulfateSalbutamol will be delivered using a Babyhaler spacer device. Ventolin will be used, brandname for Salbutamol sulfate. Ventolin contains the propellant HFA 134a. | Drug | Salbutamol |
| PlaceboAlso: Mock inhalerThe placebo will be delivered using a Babyhaler spacer device. The placebo will contain only the propellant HFA 134a. | Drug | Placebo |
Primary outcome
Course of the parent reported respiratory symptom score
Time frame: 5 days
Scores on an arbitrary ordinal scale of 0 to 3 (0= no symptoms, 1= a bit (mild), 2= quite bad (moderate), 3= very bad (severe)) are recorded by parents for wheeze, cough and difficulty in breathing for both day and night, giving a maximum possible symptom score of 18 for each day.
8 secondary outcomes
Time to recovery
Time frame: 28 days
Adverse effects
Time frame: 7 days
Health care resource use
Time frame: 28 days
Persistent wheezing on auscultation on day 5
Time frame: on day 5
Day of parent reported recovery
Time frame: 28 days
Parent satisfaction with care
Time frame: on day 28
Out-of-pocket expenses
Time frame: 14 days
Parent productivity losses
Time frame: 14 days
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jul 2021.
- Background: PubMed 18480107Matricardi PM, Illi S, Gruber C, Keil T, Nickel R, Wahn U, Lau S. Wheezing in childhood: incidence, longitudinal patterns and factors predicting persistence. Eur Respir J. 2008 Sep;32(3):585-92. doi: 10.1183/09031936.00066307. Epub 2008 May 14.
- Background: PubMed 7800004Martinez FD, Wright AL, Taussig LM, Holberg CJ, Halonen M, Morgan WJ. Asthma and wheezing in the first six years of life. The Group Health Medical Associates. N Engl J Med. 1995 Jan 19;332(3):133-8. doi: 10.1056/NEJM199501193320301.
- Background: PubMed 20855440Mallol J, Garcia-Marcos L, Sole D, Brand P; EISL Study Group. International prevalence of recurrent wheezing during the first year of life: variability, treatment patterns and use of health resources. Thorax. 2010 Nov;65(11):1004-9. doi: 10.1136/thx.2009.115188. Epub 2010 Sep 20.
- Background: PubMed 12137663Chavasse R, Seddon P, Bara A, McKean M. Short acting beta agonists for recurrent wheeze in children under 2 years of age. Cochrane Database Syst Rev. 2002;2002(3):CD002873. doi: 10.1002/14651858.CD002873.
- Individual participant dataSharing planned: Yes. We will make our data accessable for verification and future research (other researchers / spin-off projects), yet these will be shared under restrictions. Data cannot be reused without consulting the research team.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Roger AMJ Damoiseaux, Professor principal investigator
Julius Center, UMC Utrecht
Ann van den Bruel, Professor principal investigator
KU Leuven
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Salbutamol in people with Wheezing, run by UMC Utrecht.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 23 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Course of the parent reported respiratory symptom score (time frame: 5 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04584034, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jul 2021.