Schoenbuchner, Simon M, Huang, Chao, Waldron, Cherry-Ann, Thomas-Jones, Emma, Hood, Kerenza, Carrol, Enitan D 
ORCID: 0000-0001-8357-7726 and Pallmann, Philip
(2023)
Biomarker-guided duration of antibiotic treatment in children hospitalised with confirmed or suspected bacterial infection: statistical analysis plan for the BATCH trial and PRECISE sub-study.
TRIALS, 24 (1).
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Abstract
<h4>Introduction</h4>The BATCH trial is a multi-centre randomised controlled trial to compare procalcitonin-guided management of severe bacterial infection in children with current management. PRECISE is a mechanistic sub-study embedded into the BATCH trial. This paper describes the statistical analysis plan for the BATCH trial and PRECISE sub-study.<h4>Methods</h4>The BATCH trial will assess the effectiveness of an additional procalcitonin test in children (aged 72 h to 18 years) hospitalised with suspected or confirmed bacterial infection to guide antimicrobial prescribing decisions. Participants will be enrolled in the trial from randomisation until day 28 follow-up. The co-primary outcomes are duration of intravenous antibiotic use and a composite safety outcome. Target sample size is 1942 patients, based on detecting a 1-day reduction in intravenous antibiotic use (90% power, two-sided) and on a non-inferiority margin of 5% risk difference in the composite safety outcome (90% power, one-sided), while allowing for up to 10% loss to follow-up.<h4>Results</h4>Baseline characteristics will be summarised overall, by trial arm, and by whether patients were recruited before or after the pause in recruitment due to the COVID-19 pandemic. In the primary analysis, duration of intravenous antibiotic use will be tested for superiority using Cox regression, and the composite safety outcome will be tested for non-inferiority using logistic regression. The intervention will be judged successful if it reduces the duration of intravenous antibiotic use without compromising safety. Secondary analyses will include sensitivity analyses, pre-specified subgroup analyses, and analysis of secondary outcomes. Two sub-studies, including PRECISE, involve additional pre-specified subgroup analyses. All analyses will be adjusted for the balancing factors used in the randomisation, namely centre and patient age.<h4>Conclusion</h4>We describe the statistical analysis plan for the BATCH trial and PRECISE sub-study, including definitions of clinical outcomes, reporting guidelines, statistical principles, and analysis methods. The trial uses a design with co-primary superiority and non-inferiority endpoints. The analysis plan has been written prior to the completion of follow-up.<h4>Trial registration</h4>BATCH: ISRCTN11369832, registered 20 September 2017, doi.org/10.1186/ISRCTN11369832.<h4>Precise</h4>ISRCTN14945050, registered 17 December 2020, doi.org/10.1186/ISRCTN14945050.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Antimicrobial stewardship, Procalcitonin, Severe bacterial infection, Hospitalised children, Randomised controlled trial, Statistical analysis plan |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 13 Jun 2023 15:56 |
| Last Modified: | 28 Jun 2023 12:47 |
| DOI: | 10.1186/s13063-022-06956-9 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3170903 |
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