title: A randomised controlled trial of standard transfusion versus fresher red blood cell use in intensive care (TRANSFUSE): protocol and statistical analysis plan.
abstract: OBJECTIVE
  To determine if using freshest available rather than standard-issue red blood cells (RBCs) can reduce mortality in critically ill intensive care unit patients. Our study is the largest ongoing randomised controlled trial (RCT) of RBC age in critically ill patients and will help determine if the use of the freshest available RBCs should become standard policy for the critically ill.
  
  
  METHODS
  A double-blind, multicentre, Phase III RCT of 5000 adult ICU patients in Australia, New Zealand, Europe and the Middle East.
  
  
  METHODS
  Transfusion of the freshest available RBCs in place of standard-care RBCs until hospital discharge.
  
  
  METHODS
  The primary outcome measure is 90-day all-cause mortality. Secondary outcome measures are time to death, 28-day and 180-day mortality, persistent organ dysfunction combined with death, days alive and free of mechanical ventilation and renal replacement therapy, bloodstream infection in the ICU, length of stay in the ICU and in hospital, proportion of patients with febrile non-haemolytic transfusion reactions, and quality of life at Day 180.
  
  
  RESULTS
  A detailed statistical analysis plan with predefined subgroups and secondary analyses has been finalised before results being available, to ensure an unbiased final analysis.
  
  
  CONCLUSIONS
  The pragmatic protocol design has been chosen to facilitate translation of the trial results into practice. The TRANSFUSE trial will have important clinical and policy implications, regardless of the outcome.
authors.affiliation: Australian and New Zealand Intensive Care Research Centre, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, Australia. maija.kaukonen@monash.edu.
authors.forename: Kirsi-Maija
authors.initials: KM
authors.lastname: Kaukonen
authors.affiliation: Australian and New Zealand Intensive Care Research Centre, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Bailey
authors.affiliation: Australian and New Zealand Intensive Care Research Centre, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, Australia.
authors.forename: Bridget
authors.initials: B
authors.lastname: Ady
authors.affiliation: Australian and New Zealand Intensive Care Research Centre, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, Australia.
authors.forename: Cecile
authors.initials: C
authors.lastname: Aubron
authors.affiliation: Intensive Care Unit, Western Health, Melbourne, VIC, Australia.
authors.forename: Craig
authors.initials: C
authors.lastname: French
authors.affiliation: Australian and New Zealand Intensive Care Research Centre, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, Australia.
authors.forename: Dashiell
authors.initials: D
authors.lastname: Gantner
authors.affiliation: Research and Development, Australian Red Cross Blood Service, Sydney, NSW, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Irving
authors.affiliation: Australian and New Zealand Intensive Care Research Centre, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, Australia.
authors.forename: Lynne
authors.initials: L
authors.lastname: Murray
authors.affiliation: Australian and New Zealand Intensive Care Research Centre, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, Australia.
authors.forename: Alistair
authors.initials: A
authors.lastname: Nichol
authors.affiliation: Intensive Care Units, Division of Anaesthesiology and Intensive Care Medicine, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Ville
authors.initials: V
authors.lastname: Pettilä
authors.affiliation: Australian and New Zealand Intensive Care Research Centre, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, Australia.
authors.forename: Zoe
authors.initials: Z
authors.lastname: McQuilten
authors.affiliation: Australian and New Zealand Intensive Care Research Centre, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, Australia.
authors.forename: D Jamie
authors.initials: DJ
authors.lastname: Cooper
mesh_terms: D002985:Clinical Protocols; D017707:Erythrocyte Transfusion / Q000379:methods*; D006801:Humans; D057194:Intention to Treat Analysis; D012107:Research Design