Understanding RSV: Severe Disease and the Long Term Consequences

Respiratory Syncytial Virus (RSV) Clinical Trial

Official title:

REspiratory Syncytial Virus Consortium in EUrope (RESCEU):Presumed Risk Factors and Biomarkers for RSV-related Severe Disease and Related Sequelae

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03756766
• Other study ID #: OVG 2017/02
• Status: Active, not recruiting
• Start date: December 19, 2017
• Est. completion date: November 2026

Study information

• Verified date: January 2022
• Source: University of Oxford
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The study design is a case-control, sample based study. 275 cases (Group 1), infants <12 months old with RSV infection and 40 controls (Group 2), otherwise healthy infants <12 months old without RSV infection will be recruited. Samples will be taken on enrolment and for infants in Group 1; repeated at 7 weeks convalescence. There will be annual follow up by questionnaire for up to 6 years and a minimum of 1 year, depending at what stage in the study the infant is enrolled.

Description:

Human respiratory syncytial virus (RSV) causes severe disease in the very young, elderly and in high risk groups. Worldwide in 2005 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. RSV infection in childhood is associated with subsequent wheezing and asthma. These long-term sequelae pose a substantial additional burden on healthcare systems. There is a parallel need to assemble clinical resources 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.

Group 1: Infants under 12 months with an RSV infection will have nasopharyngeal swabs, blood, urine and stool samples taken at the onset of infection and again 6 - 8 weeks later, in convalescence. An online diary will be completed for 2 weeks during illness to record the participant and parent health. The participant and their family will be followed up annually by questionnaire, for a maximum of 6 years. When the study data are analysed, the infants will be subdivided into 4 further groups; healthy infants requiring hospitalisation, healthy infants not requiring hospitalisation, infants with co-morbidity, requiring hospitalisation and infants with a co-morbidity not requiring hospitalisation. Group 2: Well, healthy infants, under 12 months with no acute respiratory infection will have nasopharyngeal swab,blood, urine and stool samples taken on enrolment. They will receive a follow up contact 7 days after enrolment to assess if they have developed any illness. The participant and their family will be followed up annually by questionnaire, for a maximum of 6 years.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 315
• Est. completion date: November 2026
• Est. primary completion date: November 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A to 12 Months

Eligibility

Inclusion Criteria: All of the following must apply

• parent/carer of the infant is willing and able to give informed consent for participation in the study

• Male or female, less than 12 months of age at enrolment

• Parent has a telephone

For group 1 only:

• Hospitalised for <48 hours at enrolment or within 96 hours of onset of illness

• Live near enough to a participating study centre for the 6-8 week home visit

Exclusion Criteria:

• Infants who have received treatment for RSV infection (eg: ribavirin)

• Infants who have had prior exposure to an RSV vaccine or medication

• Infants who have received preventative therapy for RSV (eg; palivizumab)

• Infants who have received oral steroids or montelukast within 7days of enrolment on the study

Related Conditions & MeSH terms

• Respiratory Syncytial Virus (RSV)

Intervention

Diagnostic Test:
• RSV point of care testing
Patients will have 2 nasopharyngeal swabs, a nasal swab, a stool and urine taken at baseline/ enrolment and the RSV positive ARTI group will have samples repeated at 6-8weeks.

Locations

Country	Name	City	State
United Kingdom	Oxford University Hospitals NHS Trust	Oxford
United Kingdom	Oxford Vaccine Group, Centre for Clinical Vaccinology and Tropical Medicine	Oxford

Sponsors (3)

Lead Sponsor	Collaborator
University of Oxford	Innovative Medicines Initiative, Respiratory syncytial virus consortium in Europe

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Ribonucleic acid (RNA) transcripts (Transcriptomics) that are up and down regulated in severe RSV infection	Analysis of blood to determine cellular expression of RNA during a severe, acute RSV respiratory tract infection	8 weeks
Primary	Cellular protein concentration changes (proteomics) in response to severe RSV infection	Analysis of blood samples to determine how cellular protein concentrations change in response to severe RSV infection	8 weeks
Primary	Cellular metabolite concentration changes associated with severe RSV disease	Analysis of urine and blood to identify which metabolic pathways are up-regulated at a cellular level following severe RSV infection. This is determined by measuring metabolic by-products	8 weeks
Primary	The relationship between infant RSV infection of different severity and school age asthma	Symptoms of asthma, diagnosis and use of asthma medication will be measured by parental questionnaire/medical records.	Year 6
Secondary	Ribonucleic acid (RNA) transcripts that are up or down regulated and contribute to respiratory sequelae following RSV infection in infants	Analysis of blood samples will determine changes in cellular RNA associated with RSV infection.	3 years
Secondary	Cellular protein concentration changes (Proteomics) affecting respiratory sequelae following RSV infection in infants	Analysis of blood to determine how cellular protein production is up or down regulated in response to RSV infection to correlate with subsequent respiratory sequelae	3 years
Secondary	Cellular metabolite concentration changes that contribute to respiratory sequelae following RSV infection	Analysis of blood and urine to determine which cellular metabolites are produced in increasing quantities during RSV infection and which are subsequently responsible for respiratory sequelae.	3 years
Secondary	Respiratory sequelae following RSV infection in infants	Respiratory sequelae in participants will be determined by completion of a baseline questionnaire followed by an annual questionnaire for a maximum of 3 years.; The questionnaires record patient demographics, number of siblings, family history of atopy, exposure to household smoke and pets and the ability of the child and family members to complete their usual activities	3 years
Secondary	Viral load associated with mild and severe RSV disease	Nasopharyngeal swabs will be taken at baseline and at 6-8weeks to measure viral load	8 weeks
Secondary	Genetic sequence of RSV associated with mild and severe disease	Nasopharyngeal samples will be taken at baseline and at 6-8weeks do determine the genetic sequencing of the Respiratory Syncytial Virus.	8 weeks
Secondary	Cellular immune response during RSV infection	Whole blood will be used for flow cytometric cell phenotyping to determine which immune cells are activated in response to RSV	8 weeks
Secondary	Cytokine release associated with severe RSV disease	Whole blood will be used to perform intracellular cytokine staining in response to RSV infection	8 weeks
Secondary	Altered gene expression associated with severe RSV disease	Blood sampling to determine epigenetic changes associated with RSV infection	8 weeks
Secondary	RSV disease severity	This is determined using a standardized respiratory clinical severity score (ReSVinet) which is performed at baseline.; This score has 7 subscales; Feeding intolerance (Score 0-3); Medical intervention (score 0-3); Respiratory difficulty (score 0-3); Respiratory frequency (score 0-3); Presence of apnoea (either 0, or 3); General condition (score 0-3); fever (0-2) The total score is determined by adding each component part. The total score is from 0-20. A score of 0 reflects very mild disease whilst a score of 20 indicates severe disease	8 weeks
Secondary	Health care costs and resource use	This will be determined using annual questionnaires sent to participants. The questions include: visits to healthcare providers (hospital, GP), number of admissions and duration where applicable and medication use.	3 years
Secondary	Interruption to normal activities associated with RSV disease	Baseline parental questionnaire followed by 14 day symptom diary at onset of illness. Subsequent annual questionnaire for total of 3 years to determine subsequent disease sequelae.; These questionnaires record symptom severity, duration of symptoms, whether the symptoms affect activities of daily living and a record of persisting symptoms. The follow up questionnaires will extract information about subsequent respiratory symptoms (cough, wheeze), whether the participant has required subsequent review by a healthcare practitioner or been admitted to hospital and during of admission. It also records the need for ongoing medications.; The information extracted is qualitative in nature. There is no scale used for recording this information.	3 years
Secondary	Compare the incidence of asthma after RSV hospitalisation with incidence of asthma following hospitalisation for viral infections	Parental questionnaires and participant medical records	Year 4
Secondary	Compare the incidence of asthma after RSV hospitalisation with incidence of asthma following hospitalisation for viral infections	Parental questionnaires and participant medical records	Year 5
Secondary	Compare the incidence of asthma after RSV hospitalisation with incidence of asthma following hospitalisation for viral infections	Parental questionnaires and participant medical records	Year 6
Secondary	Risk factors for persistent wheeze at 3 and 6 years of age	Demographic and clinical parameters and outcomes from CRF/demographic questionnaires	Year 4
Secondary	Risk factors for persistent wheeze at 3 and 6 years of age	Demographic and clinical parameters and outcomes from CRF/demographic questionnaires	Year 5
Secondary	Risk factors for persistent wheeze at 3 and 6 years of age	Demographic and clinical parameters and outcomes from CRF/demographic questionnaires	Year 6

External Links

•   RESCEU website (coordinators of the Understanding RSV study)