Clinical trial NCT04584034: Bronchodilators for Wheeze in Young Children Presenting to Primary Care: a Randomised, Placebo-controlled, Multicentre, Parallel Group Trial
Official title: Bronchodilators for Wheeze in Young Children Presenting to Primary Care: a Randomised, Placebo-controlled, Multicentre, Parallel Group Trial
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE4
Conditions: Wheezing
Keywords: Wheeze
Viral respiratory illnesses
Pre-school age children
Primary care
General practice
Salbutamol
Bronchodilators
Therapeutic trial
Lead sponsor: UMC Utrecht
Sponsor class: OTHER
Collaborators: name: KU Leuven
name: Maastricht University Medical Center
name: Universiteit Antwerpen
name: Université de Liège
First posted: 2020-10-12
Enrollment: 0
Sex: ALL
Minimum age (years): 6
Maximum age (years): 24
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Individually randomised, placebo-controlled, multicentre, parallel group trial
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Course of the parent reported respiratory symptom score
timeFrame: 5 days
Secondary outcomes:
measure: Time to recovery
timeFrame: 28 days
measure: Adverse effects
timeFrame: 7 days
measure: Health care resource use
timeFrame: 28 days
measure: Persistent wheezing on auscultation on day 5
timeFrame: on day 5
measure: Day of parent reported recovery
timeFrame: 28 days
measure: Parent satisfaction with care
timeFrame: on day 28
measure: Out-of-pocket expenses
timeFrame: 14 days
measure: Parent productivity losses
timeFrame: 14 days
Other outcomes:
Locations:
Study officials:
affiliation: Julius Center, UMC Utrecht
name: Roger AMJ Damoiseaux, Professor
role: PRINCIPAL_INVESTIGATOR
affiliation: KU Leuven
name: Ann van den Bruel, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Martinez 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.
citation: Mallol 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.
citation: Chavasse 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.