Real-World Effectiveness of Perinatal RSV Immunoprophylaxis

NCT ID: NCT06172660

Last Updated: 2025-08-14

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 3750 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2024-10-28
• Study Completion Date: 2028-12-30

Brief Summary

The purpose of this study is to continue evaluating how well the RSV vaccines work as they are currently being used in routine clinical practice. Some of the questions that the investigators hope to answer with this study are: 1) What is the overall effectiveness of these vaccines? 2) How long does immunity last? 3) How effective are the vaccines against new strains? 3) Does the vaccine's effectiveness vary by age?

Detailed Description

This will be a large-scale case-control study aiming to evaluate the effectiveness of perinatal RSV immunoprophylaxis. Cases and controls will be identified using active surveillance in both inpatient and outpatient clinical sites of the Yale New Haven Health System. Investigators will enroll patients seeking health care for acute respiratory illness and confirm RSV infection using approved molecular assays. Data will be collected from multiple sources, including health records, interviews, immunization registries, and population-based surveys. Investigators will generate estimates of effectiveness for each type of immunization used, disaggregated by time from immunization, disease severity, and sociodemographic characteristics (Aim 1). Investigators will also perform genetic characterization of all RSV viruses in the study, monitor the genetic diversity of the virus over time, and quantify the relative effectiveness of immunoprophylaxis against various viral lineages (Aim 2). Finally, investigators will collect acute and convalescent blood from a subset of infants and employ a single-cell and multi-omics approach to study the dynamics of the innate and adaptive immune responses during RSV infection and explore the molecular mechanisms that contribute to immunoprophylaxis failure (Aim 3).

Conditions

RSV Infection

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: RETROSPECTIVE

Study Groups

ARI Cases

Cases will be defined as infants ≤12 months old who had a clinical encounter for acute respiratory illness (ARI) and tested positive for RSV using polymerase chain reaction (PCR).

Nirsevimab

Intervention Type: DRUG

Immunoprophylaxis against RSV

Healthy Controls

Healthy controls will be individually matched to enrolled vaccine failures (immunized and RSV+) by date of birth (±1 month), sex, and immunoprophylactic agent received (i.e., maternal vaccine or monoclonal antibody).

Nirsevimab

Intervention Type: DRUG

Immunoprophylaxis against RSV

ARI Controls

Controls will be individuals with ARI who test negative for RSV and will be frequency matched based on time and clinical setting.

Nirsevimab

Intervention Type: DRUG

Immunoprophylaxis against RSV

Interventions

Nirsevimab

Immunoprophylaxis against RSV

Intervention Type: DRUG

Other Intervention Names

RSV vaccines

Eligibility Criteria

Inclusion Criteria

• ≤ 12 months of age at the time of presentation for evaluation for an acute respiratory infection (ARI).
• Documentation of an ARI, which is defined as an acute onset (<10 days) illness that includes: At least two of the following symptoms: fever (measured or subjective), chills, rigors, myalgia, headache, sore throat, nausea or vomiting, diarrhea, fatigue, congestion OR any one of the following: cough, shortness of breath, difficulty breathing, olfactory disorder, taste disorder, confusion, persistent chest pain, pale, gray, hypoxia, clinical or radiographic evidence of pneumonia or respiratory distress syndrome.
• Residents of Connecticut

Exclusion Criteria

• Illness duration of >10 days at the time of respiratory specimen collection, measured from the date of the first symptom of the current acute illness.
• Parents/guardians are not able to provide informed consent

To be eligible for inclusion in the study as a healthy control, an individual must meet all of the following criteria:

• Immunized against RSV ≤ 12 months of age
• Residents of Connecticut
• Match an enrolled case that was a vaccine failure by date of birth (±1 month), sex, and immunoprophylactic agent received (i.e., maternal vaccine vs mAb).

• Maximum Eligible Age: 12 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: collaborator

Yale University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Carlos R Oliveira, MD

Role: PRINCIPAL_INVESTIGATOR

Yale University

Locations

Yale Child Health Research Center

New Haven, Connecticut, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Carlos R Oliveira, MD

Role: CONTACT

carlos.oliveira@yale.edu

203-785-5474

Facility Contacts

Research Coordinator

Role: primary

203-785-5474

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

1R01AI179874-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2000036550

Identifier Type: -

Identifier Source: org_study_id