REspiratory Syncytial Virus Consortium in EUrope (RESCEU) Study: Defining the Burden of Disease of Respiratory Syncytial Virus in Europe.
试验速览
- 阶段
- 不适用
- 发起方
- UMC Utrecht
- 入组人数
- 10,000
- 试验地点
- 5
- 主要终点
- 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.
研究概览
简要总结
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.
详细描述
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).
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- — 至 2 Weeks（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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).
排除标准
- •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.
结局指标
主要结局
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.
时间窗: 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.
Number of participants with a RSV hospitalization (hospitalization with RT-PCR confirmed RSV).
时间窗: 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.
Number of participants with an RSV infection
时间窗: 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).
次要结局
- RSV-related wheeze incidence(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.)
- RSV related wheeze sequelae(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.)
- Incidence of other respiratory pathogens(Hospitalization CRF (1 year all participants))
- Proportion of RSV in viral ARTI(active follow-up during the RSV season in the first year of life in the active cohort.)
- All cause MA-ARTI(annual questionnaire at age 1 year (all participants))
- Effect of RSV on health care cost(Questionnaires during the first year of life (all), and up to 3 years of age (active cohort, RSV+ cases))
- Effect of all-cause ARTI on health care cost(Questionnaires during the first year of life (all), and up to 3 years of age (active cohort))
- RSV related secondary bacterial infections and the use of antibiotics(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.)
- Sample collection for biomarker research (blood, nasal swab, nasopharyngeal swab, urine, faeces, buccal swab)(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.)
- Risk factors for (severe) RSV infection(Questionnaires baseline/1 year/hospitalization, for all participants)
- Effect of RSV on Health-Related Quality of Life (HRQoL)(Quality of Life is assessed at baseline, during the RSV season and after 1,2,3 years of life.)
研究者
Louis Bont
Principle investigator, Pediatric infectious disease specialist
UMC Utrecht