To validate biomarkers that are associated with severe RSV infection and respiratory sequelae.
ID
Source
Brief title
Condition
- Viral infectious disorders
- Respiratory tract infections
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Validation of biomarkers that are associated with severe RSV infection and
respiratory sequelae.
Secondary outcome
1. Dynamics of biomarkers in the upper and lower airways of children with RSV
infection and compare these with blood and with children without airway
infection
2. Validation of currently used case definitions and severity measures for RSV
infection in infants
3. Risk factors for severe RSV disease
4. Long-term sequelae of RSV infection in the first year of life
Background summary
Human respiratory syncytial virus (RSV) causes severe disease in the very
young, elderly and in high risk groups. Worldwide in 2015 there were an
estimated 34 million cases of acute lower respiratory tract infection (ALRI),
3.4 million ALRI hospitalisations and 55,000 to 199,000 deaths associated with
RSV in children <5 years old. The majority of children admitted to the hospital
with RSV are previously healthy. Although a younger age is a risk factor for
severe disease in children without comorbidities, this cannot totally explain
the difference in severity between young children of the same age. There is an
unmet need to identify the correlates of severe RSV disease for clinical
management, classification of disease severity in clinical trials and
identification of biomarkers for severe disease, which are currently lacking.
The RESCEU (Respiratory Syncytial virus Consortium in Europe) consortium, an
IMI funded effort which brought together clinicians, epidemiologists, basic
scientists, health economists, statisticians, public health professionals and
industry from across Europe to answer key research questions relating RSV,
conducted a biomarker discovery study in healthy young infants with RSV
infection in 2 prospective studies, the RESCEU infant cohort study and the
RESCEU infant case-control study. First, possible biomarkers were identified by
means of a systematic literature review. Biomarkers discovered in RESCEU
include, but are not limited to: an array of RSV antibodies, including preF,
postF and neutralizing antibodies; gene expression profiles in infant whole
blood at birth (susceptibility) as well as during disease (severity,
prognosis). Results are currently being analysed and will be prepared for
publication in the coming months.
A critical step in biomarker development is external clinical validation as
biomarkers are often identified in data-driven exploratory studies which
increase the chance of false positive associations. Therefore, they need to be
externally validated to minimise this risk and become acceptable for clinical
implementation. This is also part of the regulatory requirements before
introduction in routine care. In PROMISE we will establish a clinical study
large enough to externally validate the biomarkers identified from RESCEU as
well as those that are still being analysed. Gene expression profiles related
to neutrophil degranulation as well as innate immunity and antiviral responses
will be of specific interest for validation. The most promising candidates will
be selected for verification, based on their biological relevance, statistical
significance, and potential contribution to a clinical question (if the
potential contribution is very small, candidates that did show statistically
significance may not be developed further).
Study objective
To validate biomarkers that are associated with severe RSV infection and
respiratory sequelae.
Study design
Prospective, observational case-control study. This case-control study will
validate discovered biomarkers related to RSV infection susceptibility and
disease severity in the RESCEU case-control study and birth cohort study. For
this a validation cohort of previously healthy infants with different
severities of RSV infection and healthy infants will be compared.
Study burden and risks
Blood, respiratory, buccal, urine and stool samples will be collected at the
moment of medical attendance for RSV infection and 6-8 weeks after
infection.Controls will have only one timepoint (baseline) at which samples are
collected. In ventilated infants with RSV also broncheo-alveolar/tracheal
aspirates will be collected. In the ventilated control group only blood,
respiratory samples and broncheo-alveolar/tracheal aspirates will be collected.
A questionnaire will be completed by the parents at baseline followed by a
diary for two weeks (14 consecutive days) for RSV positive children. A yearly
questionnaire up to the age of 3 years old will be completed by the parents.
None of the study procedures is associated with any risk for serious
complications. However, there is a minimal risk of minor complications due to
study procedures (for example a nose bleed after a nose swab or bruise after
blood sampling). Bronchoalveolar/tracheal aspirate will be collected during
routine care of ventilated children, during which the ventilation tube is
regularly suctioned. The collection of urine and feces is without any risks.
This study is group related and can only be done in this patient group because
severe RSV disease is mainly seen in infants and very rare in older children
and adults.
Benefits of participating in the study: There are no particular benefits to
participating in this study, apart from knowing knowledge obtained from it may
benefit other patients in the future.
Heidelberglaan 100
Utrecht 3584 CX
NL
Heidelberglaan 100
Utrecht 3584 CX
NL
Listed location countries
Age
Inclusion criteria
• Parents/carer of infant are willing and able to give informed consent for
participation in the study.
• Less than 12 months of age at enrolment.
• Hospitalized with (suspected) RSV infection for <96 hours at enrolment or
within 96hrs of onset of illness (for those not admitted).*
* Not applicable for control infants
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:
- Known congenital or acquired immunosuppression
- Bronchopulmonary dysplasia/chronic lung disease of infancy
- Congenital heart disease*
- 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.
• Participation in another clinical study for an investigational drug within 12
weeks before entry into this study
• Parents not able to understand and communicate in the local language or
English.
* not applicable for ventilated children without airway inflammation
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 | NL78337.041.21 |