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

Wheezing Clinical Trial

— KIWI  

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04584034
• Other study ID #: NL72651
• Status: Withdrawn
• Phase: Phase 4
• Start date: September 2021
• Est. completion date: April 2023

Study information

• Verified date: July 2021
• Source: UMC Utrecht
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: April 2023
• Est. primary completion date: April 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 24 Months

Eligibility

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

Related Conditions & MeSH terms

• Respiratory Sounds
• Wheezing

Intervention

Drug:
• Salbutamol
Salbutamol will be delivered using a Babyhaler spacer device. Ventolin will be used, brandname for Salbutamol sulfate. Ventolin contains the propellant HFA 134a.
• Placebo
The placebo will be delivered using a Babyhaler spacer device. The placebo will contain only the propellant HFA 134a.

Locations

Country	Name	City	State
n/a

Sponsors (5)

Lead Sponsor	Collaborator
UMC Utrecht	KU Leuven, Maastricht University Medical Center, Université de Liège, Universiteit Antwerpen

References & Publications (4)

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;(3):CD002873. Review. — View Citation

Mallol J, García-Marcos L, Solé 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. — View 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. — View Citation

Matricardi PM, Illi S, Grüber 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. — View Citation

Outcome

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