Bronchodilators for Wheeze in Young Children Presenting to Primary Care: a Randomised, Placebo-controlled, Multicentre, Parallel Group Trial
Trial Snapshot
- Phase
- Phase 4
- Status
- Withdrawn
- Sponsor
- UMC Utrecht
- Primary Endpoint
- Course of the parent reported respiratory symptom score
Study Overview
Brief 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. 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
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 6 Months to 24 Months (Child)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
Salbutamol
Salbutamol inhalation 4x200ug daily for 7 days, delivered using a Babyhaler
Intervention: Salbutamol (Drug)
Placebo
Placebo 4 x 2 inhalations daily for 7 days, delivered using a Babyhaler
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
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.
Secondary Outcomes
- Adverse effects(7 days)
- Persistent wheezing on auscultation on day 5(on day 5)
- Time to recovery(28 days)
- Health care resource use(28 days)
- Day of parent reported recovery(28 days)
- Parent satisfaction with care(on day 28)
- Out-of-pocket expenses(14 days)
- Parent productivity losses(14 days)
Investigators
prof. dr. R.A.M.J. Damoiseaux
Full Professor, department of General Practice
UMC Utrecht