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

Sponsor

UMC Utrecht (Other)

Overall Status

Withdrawn

CT.gov ID

NCT04584034

Collaborator

KU Leuven (Other), Maastricht University Medical Center (Other), Universiteit Antwerpen (Other), Université de Liège (Other)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Wheezing	Drug: Salbutamol Drug: Placebo	Phase 4

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

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Individually randomised, placebo-controlled, multicentre, parallel group trialIndividually randomised, placebo-controlled, multicentre, parallel group trial

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Sep 1, 2021

Anticipated Primary Completion Date :

Apr 1, 2023

Anticipated Study Completion Date :

Apr 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Salbutamol Salbutamol inhalation 4x200ug daily for 7 days, delivered using a Babyhaler	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. Other Names: Ventolin β2-adrenoceptor agonist Bronchodilator Salbutamol sulfate
Placebo Comparator: Placebo Placebo 4 x 2 inhalations daily for 7 days, delivered using a Babyhaler	Drug: Placebo The placebo will be delivered using a Babyhaler spacer device. The placebo will contain only the propellant HFA 134a. Other Names: Mock inhaler

Arm

Intervention/Treatment

Active Comparator: Salbutamol

Salbutamol inhalation 4x200ug daily for 7 days, delivered using a Babyhaler

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.

Other Names:

Ventolin

β2-adrenoceptor agonist

Bronchodilator

Salbutamol sulfate

Placebo Comparator: Placebo

Placebo 4 x 2 inhalations daily for 7 days, delivered using a Babyhaler

Drug: Placebo

The placebo will be delivered using a Babyhaler spacer device. The placebo will contain only the propellant HFA 134a.

Other Names:

Mock inhaler

Outcome Measures

Primary Outcome Measures

Course of the parent reported respiratory symptom score [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 Outcome Measures

Time to recovery [28 days]
Recovery defined as a respiratory symptom score of 5 or lower indicating only trivial symptoms
Adverse effects [7 days]
Health care resource use [28 days]
Primary care physician re-consultations, medication prescriptions (e.g. antibiotics), specialist consultations and hospital admissions
Persistent wheezing on auscultation on day 5 [on day 5]
To maximise objectivity, lung sounds will be recorded (digital stethoscope) and evaluated by an expert panel at a later date
Day of parent reported recovery [28 days]
The number of the day on which parents felt their child was recovered
Parent satisfaction with care [on day 28]
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)?
Out-of-pocket expenses [14 days]
Parent reported expenses for over-the-counter medication, additional travel, parking and child care, recorded in the study diary
Parent productivity losses [14 days]
Assessed using the iMTA Productivity Cost questionnaire (iPCQ)

Eligibility Criteria

Criteria

Ages Eligible for Study:

6 Months to 24 Months

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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