Effect of palivizumab on wheezing after respiratory syncytial virus (RSV) infection

ISRCTN ISRCTN73641710
DOI https://doi.org/10.1186/ISRCTN73641710
Secondary identifying numbers NTR1023
Submission date
21/11/2008
Registration date
23/01/2009
Last edited
24/03/2020
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Respiratory
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

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

Contact information

Dr Louis Bont
Scientific

Lundlaan 6
Utrecht
3584 EA
Netherlands

Email l.j.bont@umcutrecht.nl

Study information

Study designDouble-blind randomised placebo-controlled multicentre trial with single-blind follow-up study 6 years hereafter
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Hospital
Study typeTreatment
Participant information sheet Not available in web format, please use the contact details to request a patient information sheet
Scientific titleEffect 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]
Study acronymMAKI
Study objectivesIt 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(s)Medisch Ethische Toetsingscommissie (METC) of the Universitair Medisch Centrum Utrecht, 21/07/2008
Health condition(s) or problem(s) studiedRespiratory syncytial virus bronchiolitis and post-bronchiolitis wheezing
InterventionInfants 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 typeDrug
Pharmaceutical study type(s)
PhaseNot Applicable
Drug / device / biological / vaccine name(s)Palivizumab
Primary outcome measureNumber of wheezing days during the first year of life
Secondary outcome measures1. 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 study start date01/08/2008
Completion date01/04/2017

Eligibility

Participant type(s)Healthy volunteer
Age groupChild
SexBoth
Target number of participants452
Total final enrolment429
Key inclusion criteria1. Healthy preterm infants
2. Gestational age between 32 and 35 weeks, either sex
3. Children of parents who master the Dutch language
Key exclusion criteria1. 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
Date of first enrolment01/08/2008
Date of final enrolment01/04/2017

Locations

Countries of recruitment

  • Netherlands

Study participating centre

Lundlaan 6
Utrecht
3584 EA
Netherlands

Sponsor information

University Medical Centre Utrecht (UMCU) (Netherlands)
Hospital/treatment centre

c/o Prof. dr. E.A.M Sanders
Lundlaan 6
Utrecht
3584 EA
Netherlands

Website http://www.umcutrecht.nl
ROR logo "ROR" https://ror.org/04pp8hn57

Funders

Funder type

Industry

Abbott International plc (UK) - no restrictions for publication of the research data

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Results article results 09/05/2013 Yes No
Results article results 01/04/2018 Yes No
Results article results 01/10/2020 24/03/2020 Yes No

Editorial Notes

24/03/2020: The following changes have been made:
1. Publication reference added.
2. The total final enrolment number has been added from the reference.
08/03/2018: Publication reference added.

11/03/2016: Plain English summary added.

27/06/2014: The following changes were made to the trial record:
1. The study design was changed from 'Double-blind randomised placebo-controlled multicentre trial' to 'Double-blind randomised placebo-controlled multicentre trial with single-blind follow-up study 6 years hereafter'
2. The overall trial end date was changed from 01/04/2011 to 01/04/2017.