ClinicalTrials.gov
ClinicalTrials.gov Menu

RESCEU Study: Defining the Burden of Disease of Respiratory Syncytial Virus in Europe in Infants

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03627572
Recruitment Status : Recruiting
First Posted : August 13, 2018
Last Update Posted : August 13, 2018
Sponsor:
Collaborators:
University of Oxford
University of Edinburgh
University of Turku
Servizo Galego de Saúde
Information provided by (Responsible Party):
Louis Bont, UMC Utrecht

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.


Condition or disease Intervention/treatment
RSV Infection Respiratory Syncytial Virus Infections RSV Bronchiolitis Other: No intervention

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).


Study Type : Observational
Estimated Enrollment : 10000 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: REspiratory Syncytial Virus Consortium in EUrope (RESCEU) Study: Defining the Burden of Disease of Respiratory Syncytial Virus in Europe.
Actual Study Start Date : July 21, 2017
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : December 31, 2020

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
Active cohort (N=1000)
Participants in this group will complete questionnaires at baseline (birth) and after 1-2-3 years. At baseline samples will be collected (blood/nasopharyngeal/urine/feces/buccal). During the RSV season(Oct-May) active sampling for RSV will be done when infants experience a respiratory infection.
Other: No intervention
Not applicable (no intervention)

Passive cohort (N=9000)
Parents who agree with participation in the study will be asked to fill out a questionnaire at inclusion in the first week(s) after birth and at age one year. Only children who were admitted to the hospital for ARTI during the first year of life will be followed up to the age of maximum 3 years by yearly questionnaires.
Other: No intervention
Not applicable (no intervention)




Primary Outcome Measures :
  1. 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. [ Time Frame: In the active cohort during the RSV season (Oct-May), for all participants after 1 year (questionnaire) ]
    Lower respiratory tract infection proven to be caused by RSV for which medical consultation (general practitioner/specialist/hospitalization) is required. RSV infection is confirmed using RT-PCR from a nasal swab collected by the study team in the active cohort in case of respiratory infection. In the passive cohort, this information is collected from medical data from the hospital in case of hospitalization.

  2. Number of participants with a RSV hospitalization (hospitalization with RT-PCR confirmed RSV). [ Time Frame: In the active cohort during the RSV season (Oct-May), for all participants after 1 year (questionnaire) ]
    Hospitalization for a respiratory tract infection proven to be caused by RSV. This information is collected from the hospital data. RSV must be confirmed by RT-PCR.

  3. Number of participants with an RSV infection [ Time Frame: Active cohort only, during the RSV season (Oct-May) ]
    Incidence of RSV outside of the medical setting (active cohort only). When participants experience respiratory symptoms, the study team plans a visit to perform RSV diagnostics (nasopharyngeal swab).


Secondary Outcome Measures :
  1. RSV-related wheeze incidence [ Time Frame: 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. ]
    To estimate the incidence and frequency of RSV-related wheeze up to age 3 years. Wheeze will be assessed in questionnaires during the winter season follow-up (active cohort) and after the one, two and three years of follow-up (active and passive cohort).

  2. RSV related wheeze sequelae [ Time Frame: 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. ]
    To estimate how RSV infection of different severity relates to occurence of wheeze up to age 3 years. Wheeze will be assessed in questionnaires during follow-up (active cohort) and after the one year of follow-up (active and passive cohort). Severity characteristics of wheeze are asked such as wheeze without other symptoms and medically attended wheeze.

  3. All cause MA-ARTI [ Time Frame: annual questionnaire at age 1 year (all participants) ]
    To determine the rate of all-cause medically attended (inpatient or outpatient) ARTI (active cohort).To determine mortality (RSV associated and all-cause) through all RSV seasons of follow up (all).

  4. Effect of RSV on health care cost [ Time Frame: Questionnaires during the first year of life (all), and up to 3 years of age (active cohort, RSV+ cases) ]
    To determine health care costs and health care resource use in RSV-associated and all-cause medically attended (inpatient or outpatient) ARTI patients. Data is collected on hospitalization, duration of hospitalization, treatment given (respiratory support, antibiotics) and outpatient visits.

  5. Effect of all-cause ARTI on health care cost [ Time Frame: Questionnaires during the first year of life (all), and up to 3 years of age (active cohort) ]
    To determine health care costs and health care resource use in all-cause medically attended (inpatient or outpatient) ARTI patients. Data is collected on hospitalization, duration of hospitalization, treatment given (respiratory support, antibiotics) and outpatient visits.

  6. RSV related secondary bacterial infections and the use of antibiotics [ Time Frame: 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. ]
    To determine the incidence of RSV-related secondary bacterial respiratory tract infections within 21 days after onset of RSV infection and their association with antibiotic use in hospitalized RSV ARTI patients (all children) and non-hospitalized RSV ARTI patients (active cohort).

  7. Sample collection for biomarker research (blood, nasal swab, nasopharyngeal swab, urine, faeces, buccal swab) [ Time Frame: 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. ]
    To collect clinical samples (blood, nasal swab, nasopharyngeal swab, urine, faeces, buccal swab) for biomarker analysis. 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.

  8. Incidence of other respiratory pathogens [ Time Frame: Hospitalization CRF (1 year all participants) ]
    To determine the incidence rate of other respiratory pathogens (influenza, rhinovirus, human metapneumovirus, parainfluenzavirus, etc.) associated with all medically attended (inpatient or outpatient) ARTI (active cohort).

  9. Proportion of RSV in viral ARTI [ Time Frame: active follow-up during the RSV season in the first year of life in the active cohort. ]
    To determine the proportion of viral ARTI attributable to RSV (active cohort).

  10. Risk factors for (severe) RSV infection [ Time Frame: Questionnaires baseline/1 year/hospitalization, for all participants ]
    To determine important risk factors for RSV infection. Clinical risk factors will be assessed to see their association with severe RSV infection, defined as RSV-related hospitalization.

  11. Effect of RSV on Health-Related Quality of Life (HRQoL) [ Time Frame: Quality of Life is assessed at baseline, during the RSV season and after 1,2,3 years of life. ]
    Effect of an RSV infection on the quality of life of the child and it's parents. In various questionnaires the standardized EuroQol questionnaire is used to assess the quality of life. The questionnaire contains questions on mobility, self-care, usual activities, pain/discomfort, anxiety and worries about the child, as well as a scale to assess their current health and the health of their child from 0-100 (0 being the worst health imaginable, and 100 the best health possible).


Biospecimen Retention:   Samples With DNA
  • Blood sample (serum/paxgene/whole blood)
  • Buccal sample
  • Nasopharyngeal sample (microbiome)
  • Nasopharyngeal sample (viral testing)
  • Urine sample
  • Stool sample


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   up to 2 Weeks   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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).
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03627572


Contacts
Contact: Louis Bont, Prof. Dr. +31887563776 l.bont@umcutrecht.nl
Contact: Joanne Wildenbeest, Dr. +31887563776 j.g.wildenbeest@umcutrecht.nl

Locations
Finland
Varsinais-Suomen sairaanhoitopiirin kuntayhtymä (Turku University Hospital) Recruiting
Turku, Finland, FI-20520
Contact: Terho Heikkinen, MD, PhD    +358-50-5359095    terho.heikkinen@utu.fi   
Netherlands
University Medical Centre Utrecht Recruiting
Utrecht, Netherlands, 3584 CX
Contact: Louis J Bont, MD, PhD    +3188-7554091    l.bont@umcutrecht.nl   
Contact: Joanne G Wildenbeest, MD, PhD    +3188-7563776    j.g.wildenbeest@umcutrecht.nl   
Sub-Investigator: Koos Korsten, MD         
Sub-Investigator: Roy Zuurbier, MD         
Sub-Investigator: Marlies van Houten, MD         
Spain
Servicio Galego de Saúde (SERGAS) Recruiting
Santiago De Compostela, Spain, 15706
Contact: Federico Martinón-Torres, MD, PhD    0034- 981-955093    Federico.Martinon.Torres@sergas.es   
United Kingdom
University of Edinburgh Recruiting
Edinburgh, United Kingdom
Contact: Steve Cunningham, MD, PhD    0131 536 0808    steve.cunningham@nhs.net   
Contact: Julie Baggott    0131 536 0808    Julie.Baggott@nhslothian.scot.nhs.uk   
University of Oxford, Oxford Vaccine Group Recruiting
Oxford, United Kingdom, OX3 7LE
Contact: Andrew J Pollard, Prof. MD.    0044 (0)1865 611400    andrew.pollard@paediatrics.ox.ac.uk   
Contact: Hannah Robinson    07766 922492    hannah.robinson@paediatrics.ox.ac.uk   
Sub-Investigator: Matthew Snape, MD         
Sub-Investigator: Simon Drysdale, MD         
Sponsors and Collaborators
UMC Utrecht
University of Oxford
University of Edinburgh
University of Turku
Servizo Galego de Saúde
Investigators
Principal Investigator: Louis Bont, Prof. Dr. University Medical Centre Utrecht (UMCU)

Additional Information:
Responsible Party: Louis Bont, Principle investigator, Pediatric infectious disease specialist, UMC Utrecht
ClinicalTrials.gov Identifier: NCT03627572     History of Changes
Other Study ID Numbers: 116019-1
First Posted: August 13, 2018    Key Record Dates
Last Update Posted: August 13, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: During the course of the study, individual participant data (IPD) will only be available for researchers within the consortium.

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Louis Bont, UMC Utrecht:
RESCEU (consortium)
Burden of Disease

Additional relevant MeSH terms:
Infection
Communicable Diseases
Virus Diseases
Bronchiolitis
Respiratory Syncytial Virus Infections
Bronchitis
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Tract Infections
Pneumovirus Infections
Paramyxoviridae Infections
Mononegavirales Infections
RNA Virus Infections