Statistical analysis plan for the BLING III study: a phase 3 multicentre randomised controlled trial of continuous versus intermittent β-lactam antibiotic infusion in critically ill patients with sepsis

Laurent Billot; Jeffrey Lipman; Stephen J Brett; Jan J De Waele; Menino Osbert Cotta; Joshua S Davis; Simon Finfer; Naomi E Hammond; Serena Knowles; Shay McGuinness; John Myburgh; David L Paterson; Sandra Peake; Dorrilyn Rajbhandari; Andrew Rhodes; Jason A Roberts; Claire Roger; Charudatt Shirwadkar; Therese Starr; Colman Taylor; Joel M Dulhunty; BLING III Investigators

doi:10.51893/2021.3.OA4

Statistical analysis plan for the BLING III study: a phase 3 multicentre randomised controlled trial of continuous versus intermittent β-lactam antibiotic infusion in critically ill patients with sepsis

Crit Care Resusc. 2023 Oct 18;23(3):273-284. doi: 10.51893/2021.3.OA4. eCollection 2021 Sep 6.

Authors

Laurent Billot^{1

2}, Jeffrey Lipman^{3

4

5}, Stephen J Brett^{5

6

7}, Jan J De Waele⁸, Menino Osbert Cotta^{3

4}, Joshua S Davis^{9

10}, Simon Finfer^{1

11

12}, Naomi E Hammond^{1

2

11}, Serena Knowles¹, Shay McGuinness¹³, John Myburgh^{1

2}, David L Paterson^{3

4}, Sandra Peake^{14

15

16}, Dorrilyn Rajbhandari¹, Andrew Rhodes^{17

18}, Jason A Roberts^{3

4

5}, Claire Roger⁵, Charudatt Shirwadkar¹⁹, Therese Starr³, Colman Taylor^{1

2}, Joel M Dulhunty^{3

4

20}; BLING III Investigators

Affiliations

¹ George Institute for Global Health, Sydney, NSW, Australia.
² Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia.
³ Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia.
⁴ University of Queensland, Brisbane, QLD, Australia.
⁵ Department of Anaesthesiology, Critical Care and Emergency Medicine, CHU Nîmes, University Montpellier, Nîmes, France.
⁶ Imperial College Healthcare NHS Trust, London, United Kingdom.
⁷ Department of Surgery and Cancer, Imperial College London, London, United Kingdom.
⁸ Department of Critical Care Medicine, Ghent University Hospital, Ghent, Belgium.
⁹ Global and Tropical Health Division, Menzies School of Health Research, Darwin, NT, Australia.
¹⁰ Department of Infectious Diseases, John Hunter Hospital, Newcastle, NSW, Australia.
¹¹ Malcolm Fisher Department of Intensive Care, Royal North Shore Hospital, St Leonards, NSW, Australia.
¹² School of Public Health, Imperial College London, London, United Kingdom.
¹³ Auckland City Hospital, Auckland, New Zealand.
¹⁴ Queen Elizabeth Hospital, Adelaide, SA, Australia.
¹⁵ School of Medicine, University of Adelaide, Adelaide, SA, Australia.
¹⁶ School of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, Australia.
¹⁷ St George's University Hospitals NHS Foundation Trust, London, United Kingdom.
¹⁸ St George's University of London, London, United Kingdom.
¹⁹ Blacktown Hospital, Sydney, NSW, Australia.
²⁰ Redcliffe Hospital, Brisbane, QLD, Australia.

Abstract

Background: The β-Lactam Infusion Group (BLING) III study is a prospective, multicentre, open, phase 3 randomised controlled trial comparing continuous infusion with intermittent infusion of β-lactam antibiotics in 7000 critically ill patients with sepsis. Objective: To describe a statistical analysis plan for the BLING III study. Methods: The statistical analysis plan was designed by the trial statistician and chief investigators and approved by the BLING III management committee before the completion of data collection. Statistical analyses for primary, secondary and tertiary outcomes and planned subgroup analyses are described in detail. Interim analysis by the Data Safety and Monitoring Committee (DSMC) has been conducted in accordance with a pre-specified DSMC charter. Results and conclusions: The statistical analysis plan for the BLING III study is published before completion of data collection and unblinding to minimise analysis bias and facilitate public access and transparent analysis and reporting of study findings. Trial registration:ClinicalTrials.gov Registry NCT03212990.