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

Schoenbuchner, Simon M.; Huang, Chao; Waldron, Cherry Ann; Thomas-Jones, Emma; Hood, Kerenza; Carrol, Enitan D.; Pallmann, Philip

Abstract

Introduction: 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. Methods: 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. Results: 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. Conclusion: 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. Trial registration: BATCH: ISRCTN11369832, registered 20 September 2017, doi.org/10.1186/ISRCTN11369832. PRECISE: ISRCTN14945050, registered 17 December 2020, doi.org/10.1186/ISRCTN14945050.

Citation

Schoenbuchner, S. M., Huang, C., Waldron, C. A., Thomas-Jones, E., Hood, K., Carrol, E. D., & Pallmann, P. (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), Article 364. https://doi.org/10.1186/s13063-022-06956-9

• Journal Article Type: Article
• Acceptance Date: Nov 22, 2022
• Online Publication Date: May 30, 2023
• Publication Date: Dec 1, 2023
• Deposit Date: Jul 30, 2023
• Publicly Available Date: Jul 31, 2023
• Journal: Trials
• Print ISSN: 1745-6215
• Electronic ISSN: 1745-6215
• Publisher: Springer Verlag
• Peer Reviewed: Peer Reviewed
• Volume: 24
• Issue: 1
• Article Number: 364
• DOI: https://doi.org/10.1186/s13063-022-06956-9
• Keywords: Antimicrobial stewardship; Procalcitonin; Severe bacterial infection; Hospitalised children; Randomised controlled trial; Statistical analysis plan
• Public URL: https://hull-repository.worktribe.com/output/4337549