If most of an oral Rotarix/placebo dose is spat out or vomited within minutes of administration, a single repeat dose can be administered during the same visit

If most of an oral Rotarix/placebo dose is spat out or vomited within minutes of administration, a single repeat dose can be administered during the same visit. trial will investigate whether routinely scheduling an additional dose of Rotarix for Australian Indigenous children aged 6 to 12 months old confers significantly better protection against clinically important all-cause gastroenteritis than the current two-dose schedule at 2 and 4 months old. There are two coprimary endpoints: (1) seroconversion from baseline serum anti-rotavirus immunoglobulin A (IgA) titre 20?U/mL prior to an additional dose of Rotarix/placebo to serum anti-rotavirus IgA titre 20?U/mL following the administration of the additional dose of Rotarix/placebo and (2) time from randomisation to medical attendance (up to age 36 months old) for which the primary reason is usually acute gastroenteritis/diarrhoea. Secondary endpoints include the change in anti-rotavirus IgA log titre, time to hospitalisation for all-cause diarrhoea and for rotavirus-confirmed gastroenteritis/diarrhoea, and rotavirus notification. Analysis will be based on Bayesian inference with adaptive sample size. Ethics, registration and dissemination Ethics approval has been granted by Central Australian Human Research Ethics Committee (HREC-16-426) and Human Research Ethics Committee of the Northern Territory Department of Health and Menzies School of Health Research (HREC-2016-2658). Study investigators will ensure the trial is usually conducted in accordance with the principles of the Declaration of Helsinki and with the ICH Guidelines for Good Clinical Practice. Individual RPR104632 participant consent will be obtained. Results will be disseminated via peer-reviewed publication. The trial is usually registered with Clinicaltrials.gov (“type”:”clinical-trial”,”attrs”:”text”:”NCT02941107″,”term_id”:”NCT02941107″NCT02941107) and important modifications to this protocol will be updated. Trial registration number “type”:”clinical-trial”,”attrs”:”text”:”NCT02941107″,”term_id”:”NCT02941107″NCT02941107; Pre-results. strong class=”kwd-title” Keywords: rotavirus, rotavirus vaccine, bayesian, northern territory, paediatric infectious disease & immunisation Strengths and RPR104632 limitations of this study The ORVAC study is one of the first studies to evaluate both the immunological and the clinical impact of an additional dose of oral Rotarix rotavirus vaccine administered to children between 6 and 12 months of age. This pragmatic randomised controlled trial is based on Bayesian adaptive design, an innovative trial design that uses interim analyses to inform decisions about trial progression. While Bayesian adaptive trials are becoming increasingly common, they are yet to be established and accepted as routine research practice. The pragmatic trial design conducted under real-world conditions aims to increase the likelihood that a positive trial result will LRRC63 be more rapidly translated into policy and practice in the Northern Territory. This study will not be able to capture all cases of gastroenteritis following the administration of additional dose Rotarix/placebo, only those presenting for clinical attendance; nor whether all cases of gastroenteritis presenting for medical attendance are caused by rotavirus. Introduction Rotavirus diarrhoeal disease is usually a leading cause of child mortality globally for children under 5 years of age and continues to be responsible for the death of 118?000C1?83?000 children annually, despite the availability of rotavirus RPR104632 vaccines.1 Most of these deaths occur in resource-poor settings. In RPR104632 2006, two oral rotavirus vaccinesthe human monovalent rotavirus vaccine (Rotarix) and the pentavalent human-bovine reassortant rotavirus vaccine (RotaTeq) were licensed for use, and in 2009 2009 the World Health O endorsed their use globally.2 Despite the introduction of Rotarix into the Northern Territory (NT) childhood immunisation schedule in 2006, the rate of hospitalisation for rotavirus for NT Aboriginal and Torres Strait Islander (hereafter Indigenous) children remains more than 20 times higher than the rate of hospitalisation for non-Indigenous children,3 with evidence of waning protection in the second year of life.4 Epidemics of rotavirus remain common in remote northern and central Australia, 4 5 and these epidemics have been shown to place enormous strain on remote communities and health services. 6 This reduced protection generated by oral rotavirus vaccines has also been documented in low-income, high rotavirus burden settings in Africa and Southeast Asia (50%C64%),7C9 as has evidence of waning protection in the second year of life.9 10 The reason for the suboptimal protection from oral rotavirus vaccine in these settings is not well understood, but is thought to be the result of one or more host and environmental factors.11 A number of possible determinants of poor vaccine response have been proposed including high levels of maternal derived, vaccine-neutralising anti-rotavirus antibodies, poor nutrition, intestinal microbiota dysbiosis, environmental enteropathy, high prevalence of comorbid infections such as HIV, rotavirus strain heterogeneity and genetic determinants of immune responses and susceptibility to.