TARSILA Real-World Evidence Study

Official title

Real-world Effectiveness of maTernAl RSVpreF vaccInation Against RSV-associated Acute Respiratory ilLness in Infants in BrAzil (TARSILA Study): a Multicentre, Prospective, Test-negative, Case-Control Study

Overview

The overall objective of Tarsila Study is to estimate the real-world vaccine effectiveness of maternal RSVpreF immunization during pregnancy in Brazil against medically attended (inpatient and outpatient) respiratory syncytial virus-associated acute respiratory illness in infants. To achieve this, two multicenter, prospective, test-negative case-control studies will be conducted among infants with ARI: the TARSILA Inpatient Study, evaluating hospitalized infants and the TARSILA Outpatient Study, evaluating infants managed in outpatient settings.

Detailed description

Tarsila comprises two multicenter, prospective, case-control studies using a test-negative design in Southern Brazil (states of Rio Grande do Sul, Santa Catarina, and Paraná). The Tarsila Inpatient study will enroll infants hospitalized due to acute respiratory illness and will be conducted at referral hospitals. The Tarsila Outpatient study will enroll infants with acute respiratory illness managed in outpatient settings and will be conducted at outpatient healthcare facilities. Both studies are aligned with the nationwide introduction of maternal RSVpreF vaccination in December 2025, with enrollment occurring from April, 2026 to September, 2028. In both studies, the same clinical case definition will be applied to cases and controls. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) for RSV will be prospectively performed to classify case infants (RT-qPCR positive for RSV) and control infants (RT-qPCR negative for RSV). Maternal RSVpreF vaccination status and potential confounders will be assessed through structured interviews and review of medical records.

Interventions

• Biological respiratory syncytial virus bivalent prefusion F vaccine
  For both studies, the primary exposure is maternal receipt of respiratory syncytial virus bivalent prefusion F vaccination during pregnancy in accordance with the Brazilian National Immunization Program recommendation (24⁺⁰/₇ to 36⁺⁶/₇ weeks' gestation) with the receipt of the vaccine 14 days or more before delivery.

Primary outcome measures

• Lower respiratory Tract Disease (LRTD) Hospitalization among infants aged up to 180 days (Tarsila Inpatient Study) [Time frame: Hospitalization occurring ≤180 days after birth]
• Acute respiratory illness (ARI) among infants aged up to 180 days (Tarsila Outpatient Study) [Time frame: Occurring ≤180 days after birth.]

Secondary outcome measures (4)

• Lower respiratory Tract Disease (LRTD) hospitalization among infants aged up to 180 days by subgroups (Tarsila Inpatient Study) [Time frame: Hospitalization occurring ≤180 days after birth]
• Severe Lower respiratory Tract Disease (LRTD) hospitalization among infants aged up to 180 days (Tarsila Inpatient Study) [Time frame: Hospitalization occurring ≤180 days after birth]
• Severe Lower respiratory Tract Disease (LRTD) hospitalization among infants aged up to 180 days by subgroups (Tarsila Inpatient Study) [Time frame: Hospitalization occurring ≤180 days after birth]
• Acute respiratory illness (ARI) among infants aged up to 180 days by Subgroups (Tarsila Outpatient Study) [Time frame: ARI occurring ≤180 days after birth]

Eligibility criteria

Tarsila Inpatient Study

Inclusion criteria

• Infant born in Brazil.
• Mother resident in Brazil during the related pregnancy.
• Infant date of birth 14 days or more after start of the first national RSVpreF vaccination campaign to ensure potential to have been born to an RSVpreF-vaccinated mother.
• Infant ≤360 days of age at time of RSV specimen collection.
• Infant born at ≥37 weeks of gestational age.
• Infant hospital admission for at least 24 hours with signs and symptoms meeting the case definition of ARI, defined as the presence of any of the following: nasal secretion for ≥24 hours; respiratory distress, labored breathing, or tachypnea (respiratory rate ≥60 breaths/min for infants <2 months or ≥50 breaths/min for infants 2-12 months); cough; inability to feed for any period due to respiratory symptoms; apnea; or other relevant respiratory symptoms (examples include but are not limited to wheezing, crackles, and nasal flaring).

Exclusion criteria

• Maternal or infant receipt of any other licensed or investigational RSV preventive product.
• Infant receipt of blood transfusion or other blood products containing antibodies since birth.
• Infant previously enrolled in this study.
• Lack of informed consent from the mother or the infant's legal guardian.
• Absent or inconclusive RT-qPCR result for RSV.
• Birth to a mother whose RSVpreF vaccination status could not be confirmed.

Tarsila Outpatient Study

Inclusion criteria

• Infant born in Brazil.
• Mother resident in Brazil during the related pregnancy.
• Infant date of birth 14 days or more after start of the first national RSVpreF vaccination campaign to ensure potential to have been born to an RSVpreF-vaccinated mother.
• Infant ≤360 days of age at time of RSV specimen collection.
• Infant born at ≥37 weeks of gestational age.
• Infant presentation to an outpatient healthcare facility with signs and symptoms meeting the case definition of ARI, defined as the presence of any of the following: nasal secretion for ≥24 hours; respiratory distress, labored breathing, or tachypnea (respiratory rate ≥60 breaths/min for infants <2 months or ≥50 breaths/min for infants 2-12 months); cough; inability to feed for any period due to respiratory symptoms; apnea; or other relevant respiratory symptoms (examples include but are not limited to wheezing, crackles, and nasal flaring).

Exclusion criteria

• Mother or infant receipt of any other licensed or investigational RSV preventive product.
• Infant receipt of blood transfusion or other blood products containing antibodies since birth.
• Lack of informed consent from the mother or the infant's legal guardian.
• Absent or inconclusive RT-qPCR result for RSV.
• Birth to a mother whose RSVpreF vaccination status could not be confirmed.
• Enrollment in the study within the previous 30 days. If the interval exceeds 30 days, infants will be excluded if any previous episode tested positive for RSV.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Case-control

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07445763 · CAAE 95166426.7.1001.0008

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗