Clinical trial NCT06172660: Real-World Effectiveness of Perinatal RSV Immunoprophylaxis
Official title: Real-World Effectiveness of Perinatal RSV Immunoprophylaxis
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: RSV Infection
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2023-12-15
Enrollment: 3750
Sex: ALL
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Eligible participants will include those who have a medically-attended ARI at one of the inpatient or ambulatory recruitment sites affiliated with the Yale New Haven Health System. Investigators will enroll males and females of all racial and ethnic groups meeting the inclusion criteria.

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).

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).

Primary outcomes:
measure: Overall effectiveness of RSV immunoprophylaxis
timeFrame: Up to 5 years
Secondary outcomes:
measure: Relative effectiveness of RSV immunoprophylaxis by viral groups or clades.
timeFrame: Up to 5 years
measure: Kinetics of the innate and adaptive immune responses
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale Child Health Research Center
state: Connecticut
Study officials:
affiliation: Yale University
name: Carlos R Oliveira, MD
role: PRINCIPAL_INVESTIGATOR
References: