Clinical trial NCT03621930: RESCEU Study, Defining the Burden of Disease of RSV in Older Adults
Official title: REspiratory Syncytial Virus Consortium in EUrope (RESCEU) Study: Defining the Burden of Disease of Respiratory Syncytial Virus in Older Adults in Europe.
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: RSV Infection
Respiratory Syncytial Virus Infections
Bronchiolitis
Keywords: RESCEU (consortium)
RSV
Respiratory Syncytial Virus
Lead sponsor: UMC Utrecht
Sponsor class: OTHER
Collaborators: name: Universiteit Antwerpen
name: University of Oxford
First posted: 2018-08-09
Enrollment: 1040
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Cohort of approximately 1,000 older adults (≥60 years, including approximately 500 ≥75 years). Participants will be randomly recruited from the database of general practitioners in the following countries: the Netherlands (University Medical Centre Utrecht), Belgium (University of Antwerp) and United Kingdom (University of Oxford).

Brief summary: The REspiratory Syncytial virus Consortium in EUrope (RESCEU) is an Innovative Medicine Initiative (IMI) 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. The estimated burden of disease in older adults is comparable with non-pandemic influenza A (for which a vaccine is available). 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 could soon be available on the European market. RESCEU will deliver knowledge of the incidence and burden of RSV disease 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 older adults.

Study design:

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

Study population:

Adults aged 60 years and up (n=1,000) of which approximately 50% is above 75 years of age.

Main study parameters/endpoints:

The primary endpoints of the study are;

* The incidence of RSV infection-associated ARTI.
* RSV associated medically attended (MA) ARTI.
* RSV related hospitalization.

Detailed description: In total, 1000 participants are recruited in three European countries (the Netherlands, Belgium and the United Kingdom). Participants, older adults above the age of 60 years, are recruited from general practitioners offices. Individual participants will be followed for one year (at least one winter season). For the individual participant the study procedures are described below:

Baseline visit:

Baseline visits are performed either at home or at the participating site before the start of the RSV season. The beginning of the season is to be determined per site in accordance to the local virologic surveillance reports. In general, baseline visits are performed between August and the beginning of October.

A questionnaire on demographic, social and clinical status is completed during this visit. Additionally, vital signs are recorded such as oxygen saturation, heart frequency and breathing frequency. During the baseline visit a blood sample (60 ml, serum, paxgene, whole blood) and nasopharyngeal swab (microbiome) will be collected.

Weekly follow-up during the RSV season:

From October until May participants are contacted weekly to check whether there are signs of a respiratory tract infection. If respiratory symptoms are present, the study team will perform a home visit or ask the participant to visit the site to perform a rapid Polymerase Chain Reaction (PCR)-based point of care test (POCT) for RSV using a nasopharyngeal swab. Additionally both an oro- and nasopharyngeal swab are collected for standard PCR, vital signs are recorded. Participants are asked to complete a daily dairy on respiratory symptoms, health care use and quality of life during 28 days from the moment of infection. If symptoms are not present anymore for two consecutive days, the participant can stop completing the diary.

In case of a positive RSV infection, additional sampling is performed by the study team. This consists of a nasopharyngeal swab (microbiome) and blood (Serum/PaxGene/whole blood). The same materials (minus serum and PaxGene sample) are collected again in convalescence (1-2 weeks after infection).

End of season visit:

At the end of the RSV season (May-June), again sampling is performed combined with recording vital signs. Samples collected are; blood (serum/PaxGene) and a nasopharyngeal swab (microbiome). In addition, a questionnaire will completed on respiratory symptoms, health care use, social status and quality of life.

Eligibility criteria: Inclusion Criteria:

* Male and female adults ≥60 years of age (comorbidity, including chronic heart disease is not an exclusion criterion)
* Willing and able to give written informed consent
* Willing and able to adhere to protocol-specified procedures

Exclusion Criteria:

* Unable to perform the study procedures
* Current alcohol or drug abuse or history of unsuccessfully treated alcohol or drug abuse within the past year
* Dementia
* Life expectancy less than 1 year
* Any known or suspected immunosuppressive condition, acquired or congenital, as determined by history and/or physical examination (a more detailed description/list can be found in appendix 3 of the study protocol).
* Chronic administration (defined as more than 14 continuous days) of immunosuppressants or other immune-modifying drugs within 6 months prior to study participation. The use of topical, inhaled, and nasal glucocorticoids will be permitted (a more detailed description/list can be found in appendix 3 of the study protocol).
* Previous participation in this study or in a RSV interventional trial (vaccine, antivirals).
* Planned leave/holiday during the winter season of more than 1 month in total.

Primary outcomes:
measure: Number of participants with a Reverse Transcription-Polymerase Chain Reaction (RT-PCR) confirmed RSV infection (incidence of RSV infection).
timeFrame: Data is collected during the RSV season by weekly contact and viral swab diagnostics for RSV in case of respiratory infection. Medically attended RSV will be recorded throughout the one year follow-up.
Secondary outcomes:
measure: The incidence rate of all-cause MA-ARTI or events leading to worsening of cardiorespiratory status (based on questionnaires at baseline and after one year of follow-up).
timeFrame: Data on worsening of cardiorespiratory status is collected during individual study participation of 1 year
measure: RSV-related mortality through the RSV season.
timeFrame: Data on mortality is collected during individual study participation of 1 year
measure: Non-RSV related mortality through the RSV season.
timeFrame: Data on mortality is collected during individual study participation of 1 year
measure: Health care costs for RSV-associated ARTI.
timeFrame: Data on health care costs are collected during individual study participation of 1 year
measure: Health care costs for all-cause MA-ARTI.
timeFrame: Data on health care costs are collected during individual study participation of 1 year
measure: The incidence rate of RSV-associated secondary bacterial pneumonia events
timeFrame: Data on the incidence of pneumonia are collected during individual study participation of 1 year
measure: Change in frailty over the course of study using the Groningen Frailty indicator (GFI) questionnaire.
timeFrame: Data on the change in frailty is collected during individual study participation of 1 year
measure: Sample collection for biomarker analysis to investigate possible biomarkers which are predictive of severe or complicated RSV disease in older adults
timeFrame: Samples are collected at various timepoints during the one year study participation.
Other outcomes:
Locations:
city: Antwerp
country: Belgium
facility: University of Antwerp
state: Antwerpen
city: Utrecht
country: Netherlands
facility: University Medical Centre Utrecht
city: Oxford
country: United Kingdom
facility: University of Oxford
Study officials:
affiliation: University Medical Centre Utrecht, UMCU
name: Louis J Bont, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mao Z, Li X, Korsten K, Bont L, Butler C, Wildenbeest J, Coenen S, Hens N, Bilcke J, Beutels P; RESCEU Investigators. Economic Burden and Health-Related Quality of Life of Respiratory Syncytial Virus and Influenza Infection in European Community-Dwelling Older Adults. J Infect Dis. 2022 Aug 12;226(Suppl 1):S87-S94. doi: 10.1093/infdis/jiac069.
citation: Zuurbier RP, Korsten K, Verheij TJM, Butler C, Adriaenssens N, Coenen S, Gruselle O, Vantomme V, van Houten MA, Bont LJ, Wildenbeest JG; REspiratory Syncytial Virus Consortium in EUrope (RESCEU) Investigators. Performance Assessment of a Rapid Molecular Respiratory Syncytial Virus Point-of-Care Test: A Prospective Community Study in Older Adults. J Infect Dis. 2022 Aug 12;226(Suppl 1):S63-S70. doi: 10.1093/infdis/jiab600.
citation: Korsten K, Adriaenssens N, Coenen S, Butler CC, Pircon JY, Verheij TJM, Bont LJ, Wildenbeest JG; RESCEU Investigators. Contact With Young Children Increases the Risk of Respiratory Infection in Older Adults in Europe-the RESCEU Study. J Infect Dis. 2022 Aug 12;226(Suppl 1):S79-S86. doi: 10.1093/infdis/jiab519.
citation: Korsten K, Adriaenssens N, Coenen S, Butler CC, Verheij TJM, Bont LJ, Wildenbeest JG; RESCEU Investigators. World Health Organization Influenza-Like Illness Underestimates the Burden of Respiratory Syncytial Virus Infection in Community-Dwelling Older Adults. J Infect Dis. 2022 Aug 12;226(Suppl 1):S71-S78. doi: 10.1093/infdis/jiab452.
citation: Korsten K, Adriaenssens N, Coenen S, Butler C, Ravanfar B, Rutter H, Allen J, Falsey A, Pircon JY, Gruselle O, Pavot V, Vernhes C, Balla-Jhagjhoorsingh S, Oner D, Ispas G, Aerssens J, Shinde V, Verheij T, Bont L, Wildenbeest J; RESCEU investigators. Burden of respiratory syncytial virus infection in community-dwelling older adults in Europe (RESCEU): an international prospective cohort study. Eur Respir J. 2021 Apr 1;57(4):2002688. doi: 10.1183/13993003.02688-2020. Print 2021 Apr.