Bronchodilators for Wheeze in Young Children Presenting to Primary Care: a Randomised, Placebo-controlled, Multicentre, Parallel Group Trial

Study Overview
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Brief Summary
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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
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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.

Official Title
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Bronchodilators for Wheeze in Young Children Presenting to Primary Care: a Randomised, Placebo-controlled, Multicentre, Parallel Group Trial

Conditions
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Wheezing

Intervention / Treatment
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* Drug: Salbutamol
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 24 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Individually randomised, placebo-controlled, multicentre, parallel group trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Salbutamol<br>Salbutamol inhalation 4x200ug daily for 7 days, delivered using a Babyhaler | Drug: Salbutamol<br>* Salbutamol will be delivered using a Babyhaler spacer device. Ventolin will be used, brandname for Salbutamol sulfate. Ventolin contains the propellant HFA 134a.<br>* Other names: Salbutamol sulfate;|
| Placebo Comparator: Placebo<br>Placebo 4 x 2 inhalations daily for 7 days, delivered using a Babyhaler | Drug: Placebo<br>* The placebo will be delivered using a Babyhaler spacer device. The placebo will contain only the propellant HFA 134a.<br>* Other names: Mock inhaler;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 5 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to recovery | Recovery defined as a respiratory symptom score of 5 or lower indicating only trivial symptoms | 28 days | 
| Adverse effects |  | 7 days | 
| Health care resource use | Primary care physician re-consultations, medication prescriptions (e.g. antibiotics), specialist consultations and hospital admissions | 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 | on day 5 | 
| Day of parent reported recovery | The number of the day on which parents felt their child was recovered | 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)? | 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 | 14 days | 
| Parent productivity losses | Assessed using the iMTA Productivity Cost questionnaire (iPCQ) | 14 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Wheeze, Viral respiratory illnesses, Pre-school age children, Primary care, General practice, Salbutamol, Bronchodilators, Therapeutic trial