THRIVE - Trial of Passive Humoral RSV Immunity for Value and Effectiveness

This study is a pragmatic, parallel-group, randomised controlled trial conducted in the Northern Territory to evaluate an RSV prevention strategy in Aboriginal and Torres Strait Islander infants under real-world conditions.

Eligible infants aged approximately 6 months (+90 days) will be randomised in a 1:1 ratio to receive either a single intramuscular dose of RSV-specific monoclonal antibody (nirsevimab) or standard care. Randomisation will be stratified by geographic region (e.g. Top End and Central Australia), remoteness classification and prior nirsevimab dose status.

At enrolment, baseline data is collected to confirm eligibility and characterise the study population. This includes review of immunisation and birth records and collection of simple clinical measurements such as weight and temperature, consistent with routine care.

The study is designed to minimise participant burden and reflect routine clinical practice. Apart from the study intervention and a brief follow-up contact approximately 7 days after enrolment to assess early safety, no additional procedures or scheduled study visits are required. Participants will otherwise continue to receive standard healthcare through existing services.

Outcome ascertainment will be undertaken using passive follow-up through routinely collected health data. This includes review of hospital medical records and linkage with RSV notifications reported through the Northern Territory notifiable disease surveillance system. These data sources will be used to identify laboratory-confirmed RSV infection, healthcare presentations, and hospital admissions during the follow-up period.

The study incorporates a Bayesian adaptive design, allowing for interim analyses at predefined enrolment milestones. This enables potential early stopping for superiority or futility, ensuring efficient use of resources and minimising unnecessary exposure of participants.

An economic evaluation will be conducted alongside the trial to assess the cost-effectiveness of the intervention using observed healthcare utilisation and outcome data.

Inclusion criteria

• Aboriginal and/or Torres Strait Islander infant ≥ 6 calendar months old and < 9 calendar months old.
• Parent/caregiver is willing for their infant to participate in the study and informed consent for the infant's participation in the study has been given.
• Parent/caregiver is willing to comply with all study procedures outlined in the protocol, including review of maternal/ infant immunisation records, electronic medical records and public health notifications, for the duration of the study.

Exclusion criteria

• Infants with a contra-indication to RSV-SMA per the Australian Immunisation Handbook (i.e. anaphylaxis to a prior dose).
• Infants who have received a prior dose of RSV-SMA at ≥ 3 calendar months old.
• Previously enrolled in this trial.

Temporary Exclusion Criteria

• Infants who have received a prior dose of RSV-SMA between ≥ 1 calendar months old and < 3 calendar months old will be excluded until at least 150 days have passed since their most recent dose. Randomisation can be delayed until participants meet this criterion.
• Acute illness at the time of assessment (e.g. fever ≥ 38.5°C, acute respiratory or other infection as determined by trained and delegated study staff) is temporarily excluded until they are recovered and/or symptom-free for ≥ 24 hours.