Clinical trial NCT03627572: RESCEU Study: Defining the Burden of Disease of Respiratory Syncytial Virus in Europe in Infants
Official title: REspiratory Syncytial Virus Consortium in EUrope (RESCEU) Study: Defining the Burden of Disease of Respiratory Syncytial Virus in Europe.
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: RSV Infection
Respiratory Syncytial Virus Infections
RSV Bronchiolitis
Keywords: RESCEU (consortium)
Burden of Disease
Lead sponsor: UMC Utrecht
Sponsor class: OTHER
Collaborators: name: University of Oxford
name: University of Edinburgh
name: University of Turku
name: Servicio Gallego de Salud
First posted: 2018-08-13
Enrollment: 10000
Sex: ALL
Maximum age (years): 2
Standard ages: CHILD
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Birth cohort of 10,000 healthy term infants of the general population including a nested (active) cohort of 1,000 healthy term infants. Subjects will be recruited from maternity wards during the first days after birth in the following countries: the Netherlands (UMCU), United Kingdom (UEDIN, UOXF), Spain (Sergas) and Finland (TUH).

Brief summary: The REspiratory Syncytial virus Consortium in EUrope (RESCEU) is an Innovative Medicine Initiative (IMI) effort funded by the EU 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. RESCEU will deliver knowledge of the incidence and burden of disease RSV in young children and older adults in Europe, which is essential for stakeholders (governments, etc) to take decisions about prophylaxis and treatment.

Objective:

To determine the burden of disease due to RSV in young children.

Study design:

Prospective epidemiological, observational, multi-country, multicenter cohort study.

Study population:

Birth cohort of healthy infants (follow-up from birth until the age of 3 years maximum):

* Passive birth cohort (n=9,000).
* Active birth cohort (n=1,000).

Main study parameters/endpoints:

The primary endpoint of the study is the incidence of RSV infection-associated ARTI, RSV associated medically attended (MA) ARTI (active birth cohort) and RSV related hospitalization (passive birth cohort) in infants (\< 1 year) during 3 RSV seasons. In addition, a major secondary endpoint is RSV attributable burden of wheezing.

Detailed description: This will be a multi-country, multicenter, prospective, observational cohort study conducted across 3 consecutive years to determine the incidence of RSV infection, RSV associated MA-ARTI and RSV related hospitalization in a birth cohort of healthy subjects, recruited from the general population.

At birth parents will be asked by a member of the study team to participate in the active cohort. If enrolled, a nasopharyngeal sample, a blood sample, a buccal sample, and urine and stool samples will be collected from the baby in the first week after birth. The blood sample will be collected by means of a heel prick or a venepuncture, if possible, in combination with an already scheduled moment of blood sampling. Respiratory tract symptoms will be assessed weekly during the RSV season by telephone or email or (daily) telephone app. If a child experiences a new episode of ARTI according to the parents, the study team will visit the child to collect a nasopharyngeal sample, 200µl is used to perform a point of care (POC) test for RSV, and the rest will be stored for additional viral testing by Reverse Transcription-Polymerase Chain Reaction (RT-PCR). If RSV is positive, parents will be asked informed consent to obtain additional blood, nasopharyngeal, urine and stool samples at the time of RSV infection and 6-8 weeks after RSV infection.

Parents of all children in the active cohort will be asked yearly to fill in a questionnaire until age 3 years maximum or till end of study (defined as the moment that the last included subject has been followed up for 12 months).

If parents decline to participate in the active birth cohort, informed consent will be asked for passive follow up. Parents of participants in passive follow-up will be asked to fill in a questionnaire at birth and after one year. If their child was admitted to the hospital because of an ARTI, clinical data will be collected retrospectively from the hospital. Participating hospitals will perform RSV tests as part of standard diagnostic care in children \<1 year of age who are admitted with ARTI. Only children with hospitalization due to ARTI will be followed up by a yearly questionnaire until age 3 years maximum or till end of study (defined as the moment that the last included subject has been followed up for 12 months).

Eligibility criteria: Inclusion Criteria:

* Healthy\* children, gestation age at least 37+0, born at participating centers.
* Written informed consent obtained from parents.
* Parents ability and willingness to adhere to protocol-specified procedures (active cohort).

Exclusion Criteria:

* History of clinically significant medical illness including but not limited to, cardiovascular, respiratory, renal, gastrointestinal, haematologic, neurological, endocrine, immunological, musculoskeletal, oncological or congenital disorders, as judged by the investigator. Specifically excluded examples include, but are not limited to:

  * Immunosuppressed states
  * Bronchopulmonary dysplasia/chronic lung disease of infancy
  * (clinically significant) Congenital heart disease
  * Down's syndrome
* Gestational age of less than 37+0 weeks.
* Acute severe medical condition at moment of heel prick (e.g. sepsis, severe asphyxia, for which the child is admitted to the hospital).
* Child in care.
* Parents not able to understand and communicate in the local language.
* Living outside catchment area of study sites.
* Mother vaccinated against RSV during pregnancy.

Primary outcomes:
measure: Number of participants with a Medically attended RSV acute lower respiratory tract infection (MA-RSV-ALRI) based on a positive RT-PCR for RSV who visit a clinician during the RSV-ALRI.
timeFrame: In the active cohort during the RSV season (Oct-May), for all participants after 1 year (questionnaire)
measure: Number of participants with a RSV hospitalization (hospitalization with RT-PCR confirmed RSV).
timeFrame: In the active cohort during the RSV season (Oct-May), for all participants after 1 year (questionnaire)
measure: Number of participants with an RSV infection
timeFrame: Active cohort only, during the RSV season (Oct-May)
Secondary outcomes:
measure: RSV-related wheeze incidence
timeFrame: The incidence of wheeze will be determined by annual questionnaires at age 1 year, 2 years and 3 years (active cohort and all children hospitalized for ARTI) maximum or till end of study.
measure: RSV related wheeze sequelae
timeFrame: Severity of wheeze will be determined by annual questionnaires at age 1 year, 2 years and 3 years (active cohort and all children hospitalized for ARTI) maximum or till end of study.
measure: All cause MA-ARTI
timeFrame: annual questionnaire at age 1 year (all participants)
measure: Effect of RSV on health care cost
timeFrame: Questionnaires during the first year of life (all), and up to 3 years of age (active cohort, RSV+ cases)
measure: Effect of all-cause ARTI on health care cost
timeFrame: Questionnaires during the first year of life (all), and up to 3 years of age (active cohort)
measure: RSV related secondary bacterial infections and the use of antibiotics
timeFrame: Hospitalization case report form (CRF) (1 year, all participants), active follow-up during the RSV season in the first year of life in the active cohort.
measure: Sample collection for biomarker research (blood, nasal swab, nasopharyngeal swab, urine, faeces, buccal swab)
timeFrame: This is collected at baseline (around the 5th day of life) for active participants and in case of an RSV infection during the winter season.
measure: Incidence of other respiratory pathogens
timeFrame: Hospitalization CRF (1 year all participants)
measure: Proportion of RSV in viral ARTI
timeFrame: active follow-up during the RSV season in the first year of life in the active cohort.
measure: Risk factors for (severe) RSV infection
timeFrame: Questionnaires baseline/1 year/hospitalization, for all participants
measure: Effect of RSV on Health-Related Quality of Life (HRQoL)
timeFrame: Quality of Life is assessed at baseline, during the RSV season and after 1,2,3 years of life.
Other outcomes:
Locations:
city: Turku
country: Finland
facility: Varsinais-Suomen sairaanhoitopiirin kuntayhtymä (Turku University Hospital)
city: Utrecht
country: Netherlands
facility: University Medical Centre Utrecht
city: Santiago De Compostela
country: Spain
facility: Servicio Galego de Saúde (SERGAS)
city: Edinburgh
country: United Kingdom
facility: University of Edinburgh
city: Oxford
country: United Kingdom
facility: University of Oxford, Oxford Vaccine Group
Study officials:
affiliation: University Medical Centre Utrecht (UMCU)
name: Louis Bont, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wildenbeest JG, Billard MN, Zuurbier RP, Korsten K, Langedijk AC, van de Ven PM, Snape MD, Drysdale SB, Pollard AJ, Robinson H, Heikkinen T, Cunningham S, O'Neill T, Rizkalla B, Dacosta-Urbieta A, Martinon-Torres F, van Houten MA, Bont LJ; RESCEU Investigators. The burden of respiratory syncytial virus in healthy term-born infants in Europe: a prospective birth cohort study. Lancet Respir Med. 2023 Apr;11(4):341-353. doi: 10.1016/S2213-2600(22)00414-3. Epub 2022 Nov 10.
citation: Wildenbeest JG, Zuurbier RP, Korsten K, van Houten MA, Billard MN, Derksen-Lazet N, Snape MD, Drysdale SB, Robinson H, Pollard AJ, Heikkinen T, Cunningham S, Leach A, Martinon-Torres F, Rodriguez-Tenreiro Sanchez C, Gomez-Carballa A, Bont LJ; RESCEU Investigators. Respiratory Syncytial Virus Consortium in Europe (RESCEU) Birth Cohort Study: Defining the Burden of Infant Respiratory Syncytial Virus Disease in Europe. J Infect Dis. 2020 Oct 7;222(Suppl 7):S606-S612. doi: 10.1093/infdis/jiaa310.
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.