Identification and Clinical Validation of Biomarkers Associated With Clinical Severity in Adults Infected With RSV

NCT06197152 | Recruiting

• 1 other identifier: APHP221290
• Study Type: observational
• Target: 133
• Locations: 1 country
• Sites: 1

Brief Summary

A short description, 5000 characters Intro: Respiratory Syncytial Virus (RSV) is a frequent, ubiquitous agent of respiratory viral infections. It is the leading viral cause of lower respiratory tract infection (LRTI) in infants and also causes significant morbidity and mortality in adults, especially in the elderly, in patients with cardiorespiratory comorbidities \[e.g., patients with Chronic Obstructive Pulmonary Disease (COPD) and/or heart failure\], and in immunocompromised patients. Clinical phenotyping of RSV respiratory infections has shown that the occurrence of LRTI in RSV-infected patients is associated with the need for ventilatory support and an increased risk of mortality. Virological data also suggest that there is a relationship between high nasopharyngeal viral replication levels and a poor prognosis, although these data have not been confirmed in other studies. Beyond viral load, the impact of viral subtypes on the severity of RSV infection is controversial. Few data have explored the prognostic value of genetic diversity (i.e., role of RSV variants, mutations occurring during clinical course) in RSV-infected adult patients with acute respiratory failure. Objective: The main goal of the present study is to identify and validate biomarkers associated with RSV severity in adults infected with RSV that will be useful to guide treatment decisions in the future. This study will additionally characterize the thus far unknown genetic diversity of RSV in hospitalized adults with severe and mild infections, in order to anticipate virological escape mechanisms from current and future treatments. Method: This is a prospective multicenter cohort study of patients with RSV infection admitted to the hospital. These patients will be followed-up for 28 days. Nasopharyngeal samples will be obtained sequentially (i.e., at day 0, day 3-4, day 5-7, and day 14 of inclusion) for virological and transcriptomic analyses. Blood samples will also be collected at day 0 (EDTA tubes and Paxgene tubes) for peripheral transcriptomic analyses and plasma banking. The 100 first patients included in the study will be allocated to the development cohort and the last 100 patients will be allocated to the validation cohort.

Conditions

Respiratory Syncytial Virus Infections

Keywords

Respiratory Syncytial Virus; RSV; Respiratory infection; Febrile acute respiratory syndrome; Immuno-virological determinants

Outcome Measures

Primary Outcomes (1)

• Inflammatory and immune response

  Patients with severe disease, defined as developing acute respiratory failure with a World Health Organization (WHO) ten-point scale ≥6 at any time of hospital stay, and those with mild disease (WHO ten-point scale remaining \<6 during hospital stay) will be compared using several biological tools, in particular the inflammatory and immune response assessed by transcriptomic analyses in peripheral blood and in respiratory samples (nasopharyngeal swabs and bronchoalveolar lavage fluid or tracheal aspirates when available).

  within 72h of hospitalization

Secondary Outcomes (3)

• Inflammatory and immune response during hospital stay

  during hospitalization (until day 28).

• RSV genetic variability during hospitalization

  during hospitalization (until day 28)

• RSV genetic variability at admission

  during hospitalization (within 72h of hospitalization)

Study Arms (2)

100 patients with RSV diagnosis

Patients with acute respiratory infection and positive nasopharyngeal PCR or other respiratory specimen for RSV.

Other: Nasopharyngeal swabs and biological collection

33 control patients

Patient admitted for acute respiratory syndrome with no diagnosis of respiratory infection or immunosuppression.

Other: Nasopharyngeal swabs and biological collection

Interventions

Nasopharyngeal swabs and biological collection OTHER

* Nasopharyngeal PCR * Blood and virological samples taken as part of the research will be included in a biological collection

100 patients with RSV diagnosis; 33 control patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients with RSV diagnosis : Patients hospitalized for RSV respiratory infection requiring hospital admission. Control group : patients admitted for acute respiratory failure free for RSV or any other infection.

You may qualify if:

• Age \> 18 years
• Positive RSV RT-PCR in nasopharyngeal swab
• No objection letter (from the patient or a member of family if the patient is not physically able to give consent

You may not qualify if:

• Co-infection with other respiratory viruses
• Persons under guardianship/guardianship
• AME (state medical aid) patient
• Group of "control" patients
• Age\>18 years
• Patient's consent
• Enrolled in a social security plan
• Admitted for an acute respiratory syndrome
• Negative RSV nasopharyngeal PCR (or other respiratory specimen) collected within the last 48 hours
• Persons under guardianship/guardianship
• AME (state medical aid) patient

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Intensive Care Unit Henri Mondor APHP

Créteil, 94010, France

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

Nasopharyngeal samples will be obtained sequentially (i.e., at day 0, day 3-4, day 5-7, and day 14 of inclusion) for virological and transcriptomic analyses. Blood samples will also be collected at day 0 (EDTA tubes and Paxgene tubes), day 5-7, and day 14 for peripheral transcriptomic analyses and plasma banking.

MeSH Terms

Conditions

Respiratory Syncytial Virus Infections; Respiratory Tract Infections

Condition Hierarchy (Ancestors)

Pneumovirus Infections; Paramyxoviridae Infections; Mononegavirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Diseases

Study Officials

• Pierre-André Natella, PhD

  APHP URC

  STUDY CHAIR

Central Study Contacts

Nicolas de Prost, MD, PhD

CONTACT

(+33) 1 49 81 23 94; nicolas.de-prost@aphp.fr

Slim Fourati, MD, PhD

CONTACT

(+33) 1 45 17 81 45; slim.fourati@aphp.fr

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 26, 2023
• First Posted: January 9, 2024
• Study Start: November 27, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: January 9, 2024

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)