Clinical trial NCT03756766: Understanding RSV: Severe Disease and the Long Term Consequences
Official title: REspiratory Syncytial Virus Consortium in EUrope (RESCEU):Presumed Risk Factors and Biomarkers for RSV-related Severe Disease and Related Sequelae
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Respiratory Syncytial Virus (RSV)
Lead sponsor: University of Oxford
Sponsor class: OTHER
Collaborators: name: Innovative Medicines Initiative
name: Respiratory syncytial virus consortium in Europe
First posted: 2018-11-28
Enrollment: 315
Sex: ALL
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Infants less than 12 months old who present to their GP of to hospital with RSV positive respiratory disease.

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Ribonucleic acid (RNA) transcripts (Transcriptomics) that are up and down regulated in severe RSV infection
timeFrame: 8 weeks
measure: Cellular protein concentration changes (proteomics) in response to severe RSV infection
timeFrame: 8 weeks
measure: Cellular metabolite concentration changes associated with severe RSV disease
timeFrame: 8 weeks
measure: The relationship between infant RSV infection of different severity and school age asthma
timeFrame: Year 6
Secondary outcomes:
measure: Ribonucleic acid (RNA) transcripts that are up or down regulated and contribute to respiratory sequelae following RSV infection in infants
timeFrame: 3 years
measure: Cellular protein concentration changes (Proteomics) affecting respiratory sequelae following RSV infection in infants
timeFrame: 3 years
measure: Cellular metabolite concentration changes that contribute to respiratory sequelae following RSV infection
timeFrame: 3 years
measure: Respiratory sequelae following RSV infection in infants
timeFrame: 3 years
measure: Viral load associated with mild and severe RSV disease
timeFrame: 8 weeks
measure: Genetic sequence of RSV associated with mild and severe disease
timeFrame: 8 weeks
measure: Cellular immune response during RSV infection
timeFrame: 8 weeks
measure: Cytokine release associated with severe RSV disease
timeFrame: 8 weeks
measure: Altered gene expression associated with severe RSV disease
timeFrame: 8 weeks
measure: RSV disease severity
timeFrame: 8 weeks
measure: Health care costs and resource use
timeFrame: 3 years
measure: Interruption to normal activities associated with RSV disease
timeFrame: 3 years
measure: Compare the incidence of asthma after RSV hospitalisation with incidence of asthma following hospitalisation for viral infections
timeFrame: Year 4
measure: Compare the incidence of asthma after RSV hospitalisation with incidence of asthma following hospitalisation for viral infections
timeFrame: Year 5
measure: Compare the incidence of asthma after RSV hospitalisation with incidence of asthma following hospitalisation for viral infections
timeFrame: Year 6
measure: Risk factors for persistent wheeze at 3 and 6 years of age
timeFrame: Year 4
measure: Risk factors for persistent wheeze at 3 and 6 years of age
timeFrame: Year 5
measure: Risk factors for persistent wheeze at 3 and 6 years of age
timeFrame: Year 6
Other outcomes:
Locations:
city: Oxford
country: United Kingdom
facility: Oxford University Hospitals NHS Trust
city: Oxford
country: United Kingdom
facility: Oxford Vaccine Group, Centre for Clinical Vaccinology and Tropical Medicine
Study officials:
affiliation: Oxford Vaccine Group
name: Andrew Pollard
role: STUDY_CHAIR
References:
citation: McGinley JP, Lin GL, Oner D, Golubchik T, O'Connor D, Snape MD, Gruselle O, Langedijk AC, Wildenbeest J, Openshaw P, Nair H, Aerssens J, Bont L, Martinon-Torres F, Drysdale SB, Pollard AJ; RESCEU Investigators. Clinical and Viral Factors Associated With Disease Severity and Subsequent Wheezing in Infants With Respiratory Syncytial Virus Infection. J Infect Dis. 2022 Aug 12;226(Suppl 1):S45-S54. doi: 10.1093/infdis/jiac163.
citation: Jefferies K, Drysdale SB, Robinson H, Clutterbuck EA, Blackwell L, McGinley J, Lin GL, Galal U, Nair H, Aerssens J, Oner D, Langedijk A, Bont L, Wildenbeest JG, Martinon-Torres F, Rodriguez-Tenreiro Sanchez C, Nadel S, Openshaw P, Thwaites R, Widjojoatmodjo M, Zhang L, Nguyen TL, Giaquinto C, Giordano G, Baraldi E, Pollard AJ; RESCEU Investigators. Presumed Risk Factors and Biomarkers for Severe Respiratory Syncytial Virus Disease and Related Sequelae: Protocol for an Observational Multicenter, Case-Control Study From the Respiratory Syncytial Virus Consortium in Europe (RESCEU). J Infect Dis. 2020 Oct 7;222(Suppl 7):S658-S665. doi: 10.1093/infdis/jiaa239.
citation: Lin GL, Golubchik T, Drysdale S, O'Connor D, Jefferies K, Brown A, de Cesare M, Bonsall D, Ansari MA, Aerssens J, Bont L, Openshaw P, Martinon-Torres F, Bowden R, Pollard AJ; RESCEU Investigators. Simultaneous Viral Whole-Genome Sequencing and Differential Expression Profiling in Respiratory Syncytial Virus Infection of Infants. J Infect Dis. 2020 Oct 7;222(Suppl 7):S666-S671. doi: 10.1093/infdis/jiaa448.