The ORVAC trial protocol: a phase IV, double-blind, randomised, placebo-controlled clinical trial of a third scheduled dose of Rotarix rotavirus vaccine in Australian Indigenous infants to improve protection against gastroenteritis
Introduction Rotavirus vaccines were introduced into the Australian National Immunisation Program in 2007. Despite this, Northern Territory Indigenous children continue to be hospitalised with rotavirus at a rate more than 20 times higher than non-Indigenous children in other Australian jurisdiction...
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BMJ Publishing Group
2019-11-01
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| Series: | BMJ Open |
| Online Access: | https://bmjopen.bmj.com/content/9/11/e032549.full |
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| author | Jonathan Carapetis Tom Snelling Mark A Jones Julie A Marsh Bianca Fleur Middleton Claire S Waddington Margaret Danchin Carly McCallum Sarah Gallagher Ross Andrews Carl Kirkwood Nigel Cunliffe |
| author_facet | Jonathan Carapetis Tom Snelling Mark A Jones Julie A Marsh Bianca Fleur Middleton Claire S Waddington Margaret Danchin Carly McCallum Sarah Gallagher Ross Andrews Carl Kirkwood Nigel Cunliffe |
| author_sort | Jonathan Carapetis |
| collection | DOAJ |
| description | Introduction Rotavirus vaccines were introduced into the Australian National Immunisation Program in 2007. Despite this, Northern Territory Indigenous children continue to be hospitalised with rotavirus at a rate more than 20 times higher than non-Indigenous children in other Australian jurisdictions, with evidence of waning protection in the second year of life. We hypothesised that scheduling an additional (third) dose of oral human rotavirus vaccine (Rotarix, GlaxoSmithKline) for children aged 6 to <12 months would improve protection against clinically significant all-cause gastroenteritis.Methods and analysis This Bayesian adaptive clinical 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 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 conducted in accordance with the principles of the Declaration of Helsinki and with the ICH Guidelines for Good Clinical Practice. Individual participant consent will be obtained. Results will be disseminated via peer-reviewed publication. The trial is registered with Clinicaltrials.gov (NCT02941107) and important modifications to this protocol will be updated.Trial registration number NCT02941107; Pre-results. |
| format | Article |
| id | doaj-art-acb4e71fc62e4064ac939e9ff68fc447 |
| institution | Kabale University |
| issn | 2044-6055 |
| language | English |
| publishDate | 2019-11-01 |
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| spelling | doaj-art-acb4e71fc62e4064ac939e9ff68fc4472024-11-30T16:55:09ZengBMJ Publishing GroupBMJ Open2044-60552019-11-0191110.1136/bmjopen-2019-032549The ORVAC trial protocol: a phase IV, double-blind, randomised, placebo-controlled clinical trial of a third scheduled dose of Rotarix rotavirus vaccine in Australian Indigenous infants to improve protection against gastroenteritisJonathan Carapetis0Tom Snelling1Mark A Jones2Julie A Marsh3Bianca Fleur Middleton4Claire S Waddington5Margaret Danchin6Carly McCallum7Sarah Gallagher8Ross Andrews9Carl Kirkwood10Nigel Cunliffe11Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, Nedlands, Western Australia, AustraliaWesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, West Perth, Western Australia, AustraliaWesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, West Perth, Western Australia, AustraliaWesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, West Perth, Western Australia, AustraliaGlobal and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, Northern Territory, AustraliaDepartment of Medicine, University of Cambridge School of Clinical Medicine, Cambridge, UKMurdoch Childrens Research Institute, Parkville, Victoria, AustraliaWesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, West Perth, Western Australia, AustraliaGlobal and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, Northern Territory, AustraliaOffice of the Chief Health Officer, Queensland Health, Brisbane, Queensland, AustraliaEnteric and Diarrheal Diseases, Bill and Melinda Gates Foundation, Seattle, Washington, USAClinical Infection, Microbiology and Immunology, University of Liverpool, Liverpool, UKIntroduction Rotavirus vaccines were introduced into the Australian National Immunisation Program in 2007. Despite this, Northern Territory Indigenous children continue to be hospitalised with rotavirus at a rate more than 20 times higher than non-Indigenous children in other Australian jurisdictions, with evidence of waning protection in the second year of life. We hypothesised that scheduling an additional (third) dose of oral human rotavirus vaccine (Rotarix, GlaxoSmithKline) for children aged 6 to <12 months would improve protection against clinically significant all-cause gastroenteritis.Methods and analysis This Bayesian adaptive clinical 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 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 conducted in accordance with the principles of the Declaration of Helsinki and with the ICH Guidelines for Good Clinical Practice. Individual participant consent will be obtained. Results will be disseminated via peer-reviewed publication. The trial is registered with Clinicaltrials.gov (NCT02941107) and important modifications to this protocol will be updated.Trial registration number NCT02941107; Pre-results.https://bmjopen.bmj.com/content/9/11/e032549.full |
| spellingShingle | Jonathan Carapetis Tom Snelling Mark A Jones Julie A Marsh Bianca Fleur Middleton Claire S Waddington Margaret Danchin Carly McCallum Sarah Gallagher Ross Andrews Carl Kirkwood Nigel Cunliffe The ORVAC trial protocol: a phase IV, double-blind, randomised, placebo-controlled clinical trial of a third scheduled dose of Rotarix rotavirus vaccine in Australian Indigenous infants to improve protection against gastroenteritis BMJ Open |
| title | The ORVAC trial protocol: a phase IV, double-blind, randomised, placebo-controlled clinical trial of a third scheduled dose of Rotarix rotavirus vaccine in Australian Indigenous infants to improve protection against gastroenteritis |
| title_full | The ORVAC trial protocol: a phase IV, double-blind, randomised, placebo-controlled clinical trial of a third scheduled dose of Rotarix rotavirus vaccine in Australian Indigenous infants to improve protection against gastroenteritis |
| title_fullStr | The ORVAC trial protocol: a phase IV, double-blind, randomised, placebo-controlled clinical trial of a third scheduled dose of Rotarix rotavirus vaccine in Australian Indigenous infants to improve protection against gastroenteritis |
| title_full_unstemmed | The ORVAC trial protocol: a phase IV, double-blind, randomised, placebo-controlled clinical trial of a third scheduled dose of Rotarix rotavirus vaccine in Australian Indigenous infants to improve protection against gastroenteritis |
| title_short | The ORVAC trial protocol: a phase IV, double-blind, randomised, placebo-controlled clinical trial of a third scheduled dose of Rotarix rotavirus vaccine in Australian Indigenous infants to improve protection against gastroenteritis |
| title_sort | orvac trial protocol a phase iv double blind randomised placebo controlled clinical trial of a third scheduled dose of rotarix rotavirus vaccine in australian indigenous infants to improve protection against gastroenteritis |
| url | https://bmjopen.bmj.com/content/9/11/e032549.full |
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