Respiratory Infection Virus, Respiratory Syncytial Virus (RSV)
Conditions
Keywords
Respiratory Syncytial Virus (RSV), bayesian adaptive, pragmatic clinical trial, Aboriginal and Torres Strait Islander, infants
Brief summary
RSV is a leading cause of severe respiratory illness and hospitalisation for young children, with particularly high rates of RSV respiratory infection observed amongst Aboriginal and Torres Strait Islander children living in Australia's Northern Territory. The goal of this clinical trial is to evaluate whether routinely administering a single dose of respiratory syncytial virus (RSV)-specific monoclonal antibody, nirsevimab, from 6 months old, provides protection against RSV infections for Aboriginal and Torres Strait Islander children throughout in the first and second year of life. In this study, participants will be randomly assigned to receive either a single dose of intra-muscular RSV-specific monoclonal antibody, nirsevimab, or standard care (no RSV-specific monoclonal antibody). The primary objective is to determine whether administration ofRSV-specific monoclonal antibody, nirsevimab reduces the occurrence of RSV infection over the subsequent 12 months. Secondary objectives include assessing whether nirsevimab reduces RSV-related hospital attendances, as well as respiratory and all-cause hospitalisations, over the following 6 and 12 months. An assessment of cost-effectiveness will also be undertaken. Participants will receive the study intervention at 6 months of age (+90 days). Follow-up will be conducted through passive surveillance using electronic medical records and public health notification systems to capture relevant health outcomes.
Detailed description
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.
Interventions
BIOLOGICALNirsevimab (RSV-specific monoclonal antibody)
A single intramuscular dose of RSV-specific monoclonal antibody (RSV-SMA) - nirsevimab, will be administered from 6 months old (+ 90 days) to prevent RSV respiratory infections among Aboriginal and Torres Strait Islander children in the first and second year of life. Our randomised clinical trial will be among the first to evaluate the health and economic impact of routinely administering a dose of RSV-SMA from 6 months old in a year-round program for this high-risk population with less distinct RSV infection seasons.
Sponsors
Menzies School of Health Research
University of Sydney
Murdoch Childrens Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Investigator, Outcomes Assessor)
Intervention model description
pragmatic phase IV, observer-blinded, randomised controlled trial using bayesian adaptive statistical methods
Eligibility
Sex/Gender
ALL
Age
6 Months to 9 Months
Healthy volunteers
Yes
Inclusion criteria
1. Aboriginal and/or Torres Strait Islander infant ≥ 6 calendar months old and \< 9 calendar months old. 2. 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. 3. 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
1. Infants with a contra-indication to RSV-SMA per the Australian Immunisation Handbook (i.e. anaphylaxis to a prior dose). 2. Infants who have received a prior dose of RSV-SMA at ≥ 3 calendar months old. 3. Previously enrolled in this trial. Temporary
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| RSV infection | Before 6-months and 12-months post randomisation date | RSV respiratory infection detected by reverse transcription polymerase chain reaction (RT-PCR) on a respiratory specimen from time of randomisation to before 6-months and before 12-months post-randomisation AND notified to the NT Notifiable Disease System. RSV infection before 12 months post-randomisation is the primary endpoint. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| RSV hospital attendance | Before 6-months and 12-months post randomisation date | Any emergency department presentation or hospital admission at any time from time of randomisation to before 6-months and before 12- months post-randomisation, AND for which RSV is detected by RT-PCR of a respiratory specimen (regardless of notification) collected at any time from 120 hours before hospital presentation to 72 hours afterwards. |
| RSV hospitalisation | Before 6-months and 12-months post randomisation date | Subset of RSV hospital attendances resulting in admission to an inpatient service. |
| RSV hospitalisation - severe | Before 6-months and 12-months post randomisation date. | Subset of RSV hospitalisations WITH any documented oxygen saturation \<90% at any point during the clinical presentation in accordance with the World Health Organization case definition, AND WITH documented receipt of supplemental oxygen. |
| Respiratory hospitalisation | Before 6-months and 12-months post randomisation date | Any admission to an inpatient service from time of randomisation to before 6 -months and before 12-months post randomisation AND receiving a primary diagnosis consistent with any acute respiratory infection, including bronchiolitis, bronchitis, pneumonia, influenza, whooping cough, or chest/respiratory infection, OR RSV hospitalisation. |
| Any hospitalisation | Before 6-months and 12-months post randomisation date | Hospital admission to an inpatient service at any time after time of randomisation to before 6-month and before 12-months post randomisation regardless of primary diagnosis. |
Countries
Australia
Contacts
CONTACTBianca Middleton
CONTACTSarah Gallagher
Outcome results
None listed