Optimising Rotavirus Vaccine in Aboriginal Children (ORVAC)

Australian Indigenous children, particularly those living in remote communities, suffer a disproportionately high burden of rotavirus gastroenteritis disease. Despite the introduction of rotavirus vaccine into the Northern Territory (NT) Immunisation Schedule in 2006, the rate of hospitalization for rotavirus in NT Aboriginal children \< 5 years continues to be high, and the rate ratio of rotavirus hospitalisations for Indigenous versus non-Indigenous children has actually increased. The reasons for sub-optimal vaccine response are not completely understood, but both reduced vaccine immune responses and low vaccine coverage are likely to be important factors.

This study will enrol Aboriginal infants aged 6 months to \< 12 months old who have received one or two prior doses of RV1. The coprimary aim is to determine whether an oral dose of RV1 vaccine at age 6 months to less than 12 months, compared to placebo, results in an increase in the average time to medical attendance for gastroenteritis before age 36 months (co-primary endpoint 1), and/ or superior immune protection against rotavirus gastroenteritis assessed approximately 1 to 2 months after vaccination (co-primary endpoint 2), in Australian Indigenous children.

This is a phase IV, randomised, placebo-controlled Bayesian trial with two strata representing residency based on a standard geographical classification of remoteness. It has the following key features:

1. Double-blind, randomised, placebo-controlled trial; 2. The procedures for enrolment, intervention, end-point and analysis are based on the principles of pragmatic trial design; 3. Non-fixed sample size up to 1,000 participants based on Bayesian stopping rules; 4. Fixed 1:1 enrolment into the active and control arm throughout the trial; 5. Frequent interim analyses can result in the trial stopping early for futility or expected success.