Bronchodilators for Wheeze in Young Children Presenting to Primary Care: a Randomised, Placebo-controlled, Multicentre, Parallel Group Trial (KIWI)
Primary Purpose
Wheezing
Status
Withdrawn
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
Salbutamol
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Wheezing focused on measuring Wheeze, Viral respiratory illnesses, Pre-school age children, Primary care, General practice, Salbutamol, Bronchodilators, Therapeutic trial
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Salbutamol
Placebo
Arm Description
Salbutamol inhalation 4x200ug daily for 7 days, delivered using a Babyhaler
Placebo 4 x 2 inhalations daily for 7 days, delivered using a Babyhaler
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Time to recovery
Recovery defined as a respiratory symptom score of 5 or lower indicating only trivial symptoms
Adverse effects
Health care resource use
Primary care physician re-consultations, medication prescriptions (e.g. antibiotics), specialist consultations and hospital admissions
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
Day of parent reported recovery
The number of the day on which parents felt their child was recovered
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)?
Out-of-pocket expenses
Parent reported expenses for over-the-counter medication, additional travel, parking and child care, recorded in the study diary
Parent productivity losses
Assessed using the iMTA Productivity Cost questionnaire (iPCQ)
Full Information
NCT ID
NCT04584034
First Posted
September 3, 2020
Last Updated
July 16, 2021
Sponsor
UMC Utrecht
Collaborators
KU Leuven, Maastricht University Medical Center, Universiteit Antwerpen, Université de Liège
1. Study Identification
Unique Protocol Identification Number
NCT04584034
Brief Title
Bronchodilators for Wheeze in Young Children Presenting to Primary Care: a Randomised, Placebo-controlled, Multicentre, Parallel Group Trial
Acronym
KIWI
Official Title
Bronchodilators for Wheeze in Young Children Presenting to Primary Care: a Randomised, Placebo-controlled, Multicentre, Parallel Group Trial
Study Type
Interventional
2. Study Status
Record Verification Date
July 2021
Overall Recruitment Status
Withdrawn
Why Stopped
Premature ending of the study due to impossibility of obtaining a suitable placebo-inhaler
Study Start Date
September 2021 (Anticipated)
Primary Completion Date
April 2023 (Anticipated)
Study Completion Date
April 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
UMC Utrecht
Collaborators
KU Leuven, Maastricht University Medical Center, Universiteit Antwerpen, Université de Liège
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Wheezing
Keywords
Wheeze, Viral respiratory illnesses, Pre-school age children, Primary care, General practice, Salbutamol, Bronchodilators, Therapeutic trial
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
Individually randomised, placebo-controlled, multicentre, parallel group trial
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Salbutamol
Arm Type
Active Comparator
Arm Description
Salbutamol inhalation 4x200ug daily for 7 days, delivered using a Babyhaler
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo 4 x 2 inhalations daily for 7 days, delivered using a Babyhaler
Intervention Type
Drug
Intervention Name(s)
Salbutamol
Other Intervention Name(s)
Ventolin, β2-adrenoceptor agonist, Bronchodilator, Salbutamol sulfate
Intervention Description
Salbutamol will be delivered using a Babyhaler spacer device. Ventolin will be used, brandname for Salbutamol sulfate. Ventolin contains the propellant HFA 134a.
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Mock inhaler
Intervention Description
The placebo will be delivered using a Babyhaler spacer device. The placebo will contain only the propellant HFA 134a.
Primary Outcome Measure Information:
Title
Course of the parent reported respiratory symptom score
Description
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.
Time Frame
5 days
Secondary Outcome Measure Information:
Title
Time to recovery
Description
Recovery defined as a respiratory symptom score of 5 or lower indicating only trivial symptoms
Time Frame
28 days
Title
Adverse effects
Time Frame
7 days
Title
Health care resource use
Description
Primary care physician re-consultations, medication prescriptions (e.g. antibiotics), specialist consultations and hospital admissions
Time Frame
28 days
Title
Persistent wheezing on auscultation on day 5
Description
To maximise objectivity, lung sounds will be recorded (digital stethoscope) and evaluated by an expert panel at a later date
Time Frame
on day 5
Title
Day of parent reported recovery
Description
The number of the day on which parents felt their child was recovered
Time Frame
28 days
Title
Parent satisfaction with care
Description
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)?
Time Frame
on day 28
Title
Out-of-pocket expenses
Description
Parent reported expenses for over-the-counter medication, additional travel, parking and child care, recorded in the study diary
Time Frame
14 days
Title
Parent productivity losses
Description
Assessed using the iMTA Productivity Cost questionnaire (iPCQ)
Time Frame
14 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
6 Months
Maximum Age & Unit of Time
24 Months
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Roger AMJ Damoiseaux, Professor
Organizational Affiliation
Julius Center, UMC Utrecht
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Ann van den Bruel, Professor
Organizational Affiliation
KU Leuven
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
We will make our data accessable for verification and future research (other researchers / spin-off projects), yet these will be shared under restrictions. Data cannot be reused without consulting the research team.
IPD Sharing Time Frame
Data will only be accessable after publication of trial results. Data will be stored for at least 25 years.
IPD Sharing Access Criteria
On request, after approval of principle investigator.
Citations:
PubMed Identifier
18480107
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.
Results Reference
background
PubMed Identifier
7800004
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.
Results Reference
background
PubMed Identifier
20855440
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.
Results Reference
background
PubMed Identifier
12137663
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.
Results Reference
background
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Bronchodilators for Wheeze in Young Children Presenting to Primary Care: a Randomised, Placebo-controlled, Multicentre, Parallel Group Trial
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