To establish biomarkers predictive of, or associated with severe infection caused by RSV in infants. This study aims to find biomarkers for disease susceptibility, disease severity and long-time sequelae following RSV infection. By extending follow-…
ID
Source
Brief title
Condition
- Respiratory tract infections
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is disease severity of RSV infection in the first year of
life.
Secondary outcome
1. Long term sequelae of RSV disease in the first year of life.
2. RSV viral load (copies/ml) and genetic sequence.
3. Differences in immune responses between mild and severe RSV infection.
4. Transcriptomics, proteomics, metabolomics and epigenetic signatures of mild
and severe RSV infection.
5. Storage of biological samples (respiratory, saliva, blood, stool and urine)
in a biobank.
6. Health care utilization and costs for RSV associated ARTI and long term
sequelae.
7. Applicability of found biomarkers to infants with comorbidities with RSV
infection.
Extension to six years of age part:
8. To compare the incidence of asthma after RSV hospitalization with the
incidence of asthma after milder RSV infection.
9. To compare the incidence of asthma after RSV hospitalization with the
incidence of asthma after hospitalization due to other viral infections.
10. Determine the risk factors for persistent wheezing at the age of 3 and 6
years.
Background summary
The REspiratory Syncitial virus Consortium in EUrope (RESCEU) is an Innovative
Medicine Initiative (IMI) effort funded by the EU and EFPIA under the H2020
framework to define and understand the burden of disease caused by human
respiratory syncytial virus (RSV) infection. RSV causes severe disease in
individuals at the extremes of the age spectrum and in high risk groups. It was
estimated that RSV was associated with 34 million cases of acute respiratory
tract infection (ARTI), 3.4 million ARTI hospitalizations and 55,000 to 199,000
deaths in children <5 years in 2005 worldwide. These estimates were based on
limited data and there is a substantial gap in knowledge on morbidity and
associated healthcare and social costs in Europe. New vaccines and therapeutics
against RSV are in development and will soon be available on the European
market.
The RESCEU case-control study is designed to investigate biomarkers for
severity of disease caused by RSV. We have prioritised biomarker investigation
based on key knowledge gaps that will facilitate improved understanding of the
biology of RSV infection and its sequelae as well as better control and
treatment of RSV infections. There is an urgent need to better define
correlates of protection and we therefore prioritise analysis of potential
serological biomarkers of protection in infants (using functional and total
antibody assays). We will use virological sequencing and host transcriptomics
to investigate phenotypic differences in each of our populations that may
account for severity, susceptibility and sequelae of RSV. Findings from these
analyses may identify mechanistic pathways involved in protection or the
development of sequelae and provide targets for therapeutic intervention and/or
monitoring in interventional treatment trials. We will also examine other key
*omics* approaches to biomarker discovery including proteomics, microbiome
studies, metabolomics, and epigenetic studies.
RSV infection is known to be associated with recurrent wheezing in the first
year of life. It is still unclear whether RSV infection at a young age is
associated with the development of asthma at school age and the mechanisms of
this possible association.
Study objective
To establish biomarkers predictive of, or associated with severe infection
caused by RSV in infants. This study aims to find biomarkers for disease
susceptibility, disease severity and long-time sequelae following RSV
infection.
By extending follow-up to school age (6 years), we expect to gain important
information on the association between RSV infection in the first year of life
and the subsequent development of asthma.
Study design
Prospective observational, multicentre, multicountry case-control study.
Study burden and risks
A blood, nasal, buccal, urine and stool sample will be collected at the moment
of infection and 6-8 weeks after infection. The 80 healthy controls will have
only one moment (baseline) at which samples are collected. A questionnaire will
be completed by the parents at baseline followed by a diary for two weeks (14
consecutive days). A yearly questionnaire up to the age of 3 years old will be
completed by the parents. There are few risks of participating in the study.
Blood and respiratory sampling can be associated with minor local effects, for
example, discomfort, bruising or nose bleeds. There are no risks associated
with collection of urine or stool samples.
There are no particular benefits to participating in this study, apart from
knowing knowledge obtained from it may benefit other patients in the future.
Extension until 6 year of age
Parent of participating children will complete a questionnaire after 4, 5 and 6
years. If there has been a hospital admission due to respiratory complaints in
the last year, data from this specific admission will be collected after
permission from the parents. There are no direct benefits to participating. The
results of the study may contribute to better knowledge about the disease
burden of RSV, which is important for future treatment or implementation of
prevention strategies.
Heidelberglaan 100
Utrecht 3584 CX
NL
Heidelberglaan 100
Utrecht 3584 CX
NL
Listed location countries
Age
Inclusion criteria
• Parent/carer of infant is willing and able to give informed consent for
participation in the study.
• Male or female, and less than 12 months of age at enrolment.
• Parent has a telephone.
• Hospitalized for <48 hours at enrolment or within 96hrs of onset of illness
(for those not admitted).*
• Live near enough to a participating study centre for the 6-8 week home
visit/hospital appointment to be feasible.*, * not applicable for healthy
control infants (group 2)
Inclusion criteria - Extension until 6 years of age
- Participants from Group 1a (previously healthy infants hopsitalized with RSV)
and Group 1b (previously healthy with RSV infection that did not require
admission).
- Informed consent obtained from parents
Exclusion criteria
• History of concurrent clinically significant medical illness (not directly
attributable to RSV infection) including but not limited to, cardiovascular,
respiratory, renal, gastrointestinal, haematology, neurology, endocrinology,
immunology, musculoskeletal, oncological or congenital disorders, as judged by
the investigator*
Specifically excluded examples include, but are not limited to:
o Immunosuppressed states
o Bronchopulmonary dysplasia/chronic lung disease of infancy
o Congenital heart disease
o Down*s syndrome
• Prematurity, as defined as gestational age <37 weeks at birth.*
• History of receipt of medication to treat RSV infection (e.g. ribavirin).
• Prior exposure to an RSV investigational vaccine or medication.
• History of receipt of immunoglobulin or monoclonal antibodies (including
palivizumab).
• Use of steroids or montelukast within 7 days of enrolment in the study.
• Parents not able to communicate in the local language or English.
* Inclusion criteria (and/or) for exploratory group of RSV infected infants
with comorbidity (group 1c and 1d)
Exclusion criteria - Extension study until 6 years of age:
- None
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL62657.041.17 |