Plain English Summary
Background and study aims
Respiratory syncytial virus (RSV) is a very common virus that leads to mild, cold-like symptoms in adults and older healthy children. It is not known whether recurrent wheezing in preterm children is caused by RSV infection, or whether RSV infection is just the first indication of chronic airway disease that would develop anyway. This study aims to find out by investigating whether prevention of RSV using the drug palivizumab results in a decreased incidence of recurrent wheeze.
Who can participate?
Healthy preterm infants (gestational age between 32 and 35 weeks)
What does the study involve?
Infants are randomly allocated to receive one-monthly intramuscular injections (into a muscle) of either palivizumab or a placebo (dummy) drug from discharge until the end of the RSV season, with a maximum of five injections. Number of wheezing days are recorded during the first year of life, and questionnaires are completed at age 1, 3 and 6 years. Throat swabs are taken for viral analysis during the RSV season in case of a runny nose or mild cough. These samples are tested for viruses, to determine whether the child is infected with RSV and/or other viruses. Lung function is tested and asthma-related breathing symptoms are measured by questionnaire at age 6 years.
What are the possible benefits and risks of participating?
Not provided at time of registration
Where is the study run from?
University Medical Centre Utrecht (UMCU) (Netherlands)
When is the study starting and how long is it expected to run for?
August 2008 to April 2017
Who is funding the study?
Abbott International plc (UK)
Who is the main contact?
Dr Louis Bont
l.j.bont@umcutrecht.nl
Trial website
Contact information
Type
Scientific
Primary contact
Dr Louis Bont
ORCID ID
Contact details
Lundlaan 6
Utrecht
3584 EA
Netherlands
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l.j.bont@umcutrecht.nl
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
NTR1023
Study information
Scientific title
Effect of palivizumab on respiratory syncytial virus-associated burden of disease: a randomised controlled trial [Effect van palivizumab op lange termijn gevolgen veroorzaakt door het respiratoir syncytieel virus: een gerandomiseerde placebo-gecontroleerd onderzoek]
Acronym
MAKI
Study hypothesis
It is not known whether recurrent wheeze in preterm children is caused by respiratory syncytial virus (RSV) infection (serial hypothesis) or that RSV infection is the first indication of chronic airway morbidity that would develop anyway (parallel hypothesis). This study aims to distinguish between these two hypotheses by investigating whether prevention of RSV (by palivizumab) results in decreased incidence of recurrent wheeze.
Ethics approval
Medisch Ethische Toetsingscommissie (METC) of the Universitair Medisch Centrum Utrecht, 21/07/2008
Study design
Double-blind randomised placebo-controlled multicentre trial with single-blind follow-up study 6 years hereafter
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details to request a patient information sheet
Condition
Respiratory syncytial virus bronchiolitis and post-bronchiolitis wheezing
Intervention
Infants will receive one-monthly intramuscular palivizumab 15 mg/kg or placebo from discharge until the end of the RSV season with a maximum of five injections.
Intervention type
Drug
Phase
Not Applicable
Drug names
Palivizumab
Primary outcome measures
Number of wheezing days during the first year of life
Secondary outcome measures
1. Questionnaire-reported wheezing, health-related quality of life and health-economic consequences of RSV at age 1, 3 and 6 years
2. Nasopharyngeal swabs for viral analysis during the RSV season in case of a runny nose or mild cough. These samples will be tested for viruses, to determine if the child is infected with RSV and/or other viruses. It is emphasised that RSV infection is not part of the endpoint of this study.
Added 27/06/2014:
3. Lung function at age 6 years
4. Questionnaire-reported asthma-related respiratory symptoms (ISAAC questionnaire) at age 6 years
Updated 07/03/2017:
3. Lung function measured by spirometry at age 6 years with FEV0.5 as primary endpoint
4. Asthma-related respiratory symptoms measured by ISAAC questionnaire at age 6 years with current asthma as primary endpoint. Current asthma is defined as wheeze in the past 12 months and/or use of asthma medication in the past 12 months
Overall trial start date
01/08/2008
Overall trial end date
01/04/2017
Reason abandoned
Eligibility
Participant inclusion criteria
1. Healthy preterm infants
2. Gestational age between 32 and 35 weeks, either sex
3. Children of parents who master the Dutch language
Participant type
Healthy volunteer
Age group
Child
Gender
Both
Target number of participants
452
Participant exclusion criteria
1. A known cardiac anomaly, Down's syndrome or other serious congenital disorders
2. Require intensive respiratory treatment, defined as surfactant treatment or at least 2 weeks of mechanical ventilation
3. Greater than 6 months of age at the start of the RSV season, defined as 1st October of the year of birth
4. Airway morbidity before the start of the RSV season, monitored before the first injection
Recruitment start date
01/08/2008
Recruitment end date
01/04/2017
Locations
Countries of recruitment
Netherlands
Trial participating centre
Lundlaan 6
Utrecht
3584 EA
Netherlands
Sponsor information
Organisation
University Medical Centre Utrecht (UMCU) (Netherlands)
Sponsor details
c/o Prof. dr. E.A.M Sanders
Lundlaan 6
Utrecht
3584 EA
Netherlands
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Industry
Funder name
Abbott International plc (UK) - no restrictions for publication of the research data
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary
2013 results in: http://www.ncbi.nlm.nih.gov/pubmed/23656644
2018 results in: http://www.ncbi.nlm.nih.gov/pubmed/29500030
Publication citations
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Results
Blanken MO, Rovers MM, Molenaar JM, Winkler-Seinstra PL, Meijer A, Kimpen JL, Bont L, , Respiratory syncytial virus and recurrent wheeze in healthy preterm infants., N. Engl. J. Med., 2013, 368, 19, 1791-1799, doi: 10.1056/NEJMoa1211917.