TARGET Protein: the effect of augmented administration of enteral protein to critically ill adults on clinical outcomes—statistical analysis plan for a cluster randomized, cross-sectional, double cross-over, clinical trial
Sophie Zaloumis,
Matthew J. Summers,
Jeffrey J. Presneill,
Rinaldo Bellomo,
Lee-anne S. Chapple,
Marianne J. Chapman,
Adam M. Deane,
Suzie Ferrie,
Craig French,
Sally Hurford,
Nima Kakho,
Matthew J. Maiden,
Stephanie N. O’Connor,
Sandra L. Peake,
Emma J. Ridley,
An Tran-Duy,
Patricia J. Williams,
Paul J. Young,
Amalia Karahalios,
on behalf of the TARGET Protein Investigators, the Australian, New Zealand Intensive Care Society Clinical Trials Group
Affiliations
Sophie Zaloumis
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne
Matthew J. Summers
Intensive Care Unit, Royal Adelaide Hospital
Jeffrey J. Presneill
Australian and New Zealand Intensive Care Research Centre, Monash University
Rinaldo Bellomo
Australian and New Zealand Intensive Care Research Centre, Monash University
Lee-anne S. Chapple
Intensive Care Unit, Royal Adelaide Hospital
Marianne J. Chapman
Intensive Care Unit, Royal Adelaide Hospital
Adam M. Deane
Discipline of Acute Care Medicine, The University of Adelaide
Suzie Ferrie
Department of Nutrition & Dietetics, Royal Prince Alfred Hospital
Craig French
Intensive Care Unit, Sunshine Hospital
Sally Hurford
Medical Research Institute of New Zealand
Nima Kakho
Intensive Care Unit, University Hospital Geelong
Matthew J. Maiden
Department of Critical Care, The University of Melbourne
Stephanie N. O’Connor
Intensive Care Unit, Royal Adelaide Hospital
Sandra L. Peake
Discipline of Acute Care Medicine, The University of Adelaide
Emma J. Ridley
Australian and New Zealand Intensive Care Research Centre, Monash University
An Tran-Duy
Methods and Implementation Support for Clinical and Health (MISCH) Research Hub, Faculty of Medicine, Dentistry, and Health Sciences, University of Melbourne
Patricia J. Williams
Discipline of Acute Care Medicine, The University of Adelaide
Paul J. Young
Department of Critical Care, The University of Melbourne
Amalia Karahalios
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne
on behalf of the TARGET Protein Investigators, the Australian, New Zealand Intensive Care Society Clinical Trials Group
Abstract Background The TARGET Protein trial will evaluate the effect of greater enteral protein delivery (augmented protein) on clinical outcomes of critically ill adult patients when compared to usual care. Objective To describe the statistical analysis plan for the TARGET Protein trial. Methods TARGET Protein is a cluster randomized, cross-sectional, double cross-over, open-label, registry-embedded, pragmatic clinical trial conducted across Australia and New Zealand. The trial randomized eight intensive care units (ICU) to receive enteral formula containing either higher dose enteral protein (augmented protein) or usual dose protein in a 1:1 ratio. Each ICU received one trial formula for a 3-month period and then switched to the alternate formulae. This sequence was repeated, for a total trial length of 12 months. The primary outcome is the number of days free of the index hospital and alive at day 90. Secondary outcomes include proportion of patients alive at day 90, survivor-only analysis of days free of the index hospital at day 90, duration of invasive ventilation, ICU and hospital length of stay, incidence of tracheostomy insertion, renal replacement therapy, and discharge destination. The statistical methods and models which will be used to estimate the effects for the primary and secondary outcomes are described. All statistical models will account for the cluster-randomized cross-over design to ensure correct estimation of the 95% confidence intervals. Trial enrolment is complete with 3412 patients enrolled. Data linkage is ongoing. Conclusion This statistical analysis plan enables transparent reporting of the TARGET Protein trial. It will reduce the risk of potential selective reporting biases. Trial registration Australian New Zealand Clinical Trials Registry (ACTRN12621001484831). Registered on November 1, 2021.
