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Open Access 01-12-2020 | Update

The ORVAC trial: 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: a statistical analysis plan

Authors: Mark A Jones, Todd Graves, Bianca Middleton, James Totterdell, Thomas L Snelling, Julie A Marsh

Published in: Trials | Issue 1/2020

Abstract

Objective

The purpose of this double-blind, randomised, placebo-controlled, adaptive design trial with frequent interim analyses is to determine if Australian Indigenous children, who receive an additional (third) dose of human rotavirus vaccine (Rotarix, GlaxoSmithKline) for children aged 6 to < 12 months, would improve protection against clinically significant all-cause gastroenteritis.

Participants

Up to 1000 Australian Aboriginal and Torres Strait Islander (hereafter Indigenous) infants aged 6 to < 12 months will be recruited from all regions of the Northern Territory.

Interventions

The intervention is the addition of a third scheduled dose of human monovalent rotavirus vaccine.

Co-primary and secondary outcome measures

ORVAC has two co-primary outcomes: (1) anti-rotavirus IgA seroconversion, defined as serum anti-rotavirus IgA ≥ 20 U/ml 28 to 55 days post Rotarix/placebo, and (2) time from randomisation to medical attendance for which the primary reason for presentation is acute gastroenteritis or acute diarrhoea illness before age 36 months. Secondary outcomes include (1) change in anti-rotavirus IgA log titre, (2) time from randomisation to hospitalisation with primary admission code presumed or confirmed acute diarrhoea illness before age 36 months, (3) time from randomisation to hospitalisation for which the admission is rotavirus confirmed diarrhoea illness before age 36 months and (4) time from randomisation to rotavirus infection (not necessarily requiring hospitalisation) meeting the jurisdictional definition before age 36 months.

Discussion

A detailed, prospective statistical analysis plan is presented for this Bayesian adaptive design. The plan was written by the trial statistician and details the study design, pre-specified adaptative elements, decision thresholds, statistical methods and the simulations used to evaluate the operating characteristics of the trial. As at August 2020, four interim analyses have been run, but no stopping rules have been triggered. Application of this SAP will minimise bias and supports transparent and reproducible research.

Trial registration

Clinicaltrials.gov NCT02941107. Registered on 21 October 2016

Original protocol for the study

https://doi.org/10.1136/bmjopen-2019-032549

Available only for authorised users

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Title: The ORVAC trial: 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: a statistical analysis plan
Authors: Mark A Jones
Todd Graves
Bianca Middleton
James Totterdell
Thomas L Snelling
Julie A Marsh
Publication date: 01-12-2020
Publisher: BioMed Central
Published in: Trials / Issue 1/2020
Electronic ISSN: 1745-6215
DOI: https://doi.org/10.1186/s13063-020-04602-w

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

The ORVAC trial: 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: a statistical analysis plan

Abstract

Objective

Participants

Interventions

Co-primary and secondary outcome measures

Discussion

Trial registration

Original protocol for the study

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Objective

Participants

Interventions

Co-primary and secondary outcome measures

Discussion

Trial registration

Original protocol for the study

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