ANZICS CTG Endorsed Study
TRANSFUSE
Standard issue transfusion versus fresher red blood cell use in intensive care – a randomised controlled trial
Background/context
The transfusion of stored red-blood cells is a common medical intervention. In Australia, red-blood cells are currently stored for up to 42 days prior to administration. During this period, stored red-blood cells undergo structural, biochemical and metabolic changes that are collectively known as storage lesion. Storage lesion has been associated with increased patient morbidity and mortality. Consequently, the duration of red-cell storage has, in some jurisdictions, already been reduced to 35 days, and some have planned to provide fresher blood. There have also been calls for the administration of fresh or fresher red cells to specific patient populations. This would naturally have massive stock and financial implications. Previous randomised controlled trials had limitations that reduced their capacity to detect small yet important signals for harm and to evaluate key subgroups.
The study
TRANSFUSE was an international, multicentre, randomised, double-blind trial conducted at 59 centres in five countries (Australia, New Zealand, Finland, Ireland and Saudi Arabia) that randomised 4994 critically ill patients to receive either the freshest available, compatible, allogeneic red cells (short-term storage group) or standard issue (oldest available) compatible allogeneic red cells (long-term storage group). The primary outcome was 90-day mortality. At 90 days, there were 610 deaths (24.8%) in the short-term storage group and 594 (24.1%) in the long-term storage group (absolute risk difference, 0.7 percentage points; 95% confidence interval [CI], −1.7 to 3.1; P = 0.57). Most of the pre-specified secondary measures showed no significant between-group differences in outcome. The TRANSFUSE trial demonstrated that the age of transfused red cells did not affect 90-day mortality in critically ill adults.
Significance of these results
The TRANSFUSE trial has refuted concerns regarding the safety of transfused older red-blood cells. TRANSFUSE indicates that practices which may significantly reduce the availability of blood for transfusion (a reduction in storage time to 35 days or that for certain patient populations “fresh is best”) are not required and potentially counterproductive. The TRANSFUSE trial provides high-level evidence to policy makers, clinicians and the community that the current storage and allocation processes of allogeneic red blood cells for transfusion are safe.
Management Committee
D. Jamie Cooper (Chair), Bridget Ady, Cécile Aubron, Michael Bailey, Rinaldo Bellomo, Craig French, Dashiell Gantner, David Irving, Maija Kaukonen, Colin McArthur, Zoe McQuilten, Phillip Mondy, Lynne Murray, Alistair Nichol, Neil Orford, Ville Pettilä, Louise Phillips, Jeffrey Presneill, Michael Reade, Shirley Vallance, and Andrew Webb.
Administering Institution
ANZIC Research Centre, Monash University
Australian Clinical Trials Alliance (ACTA) Trial of the Year Award Finalist
The TRANSFUSE trial was a finalist in the ACTA Trial of the Year Award, presented by the Federal Health Minister Greg Hunt, for an investigator-driven trial that addressed a critical gap in the evidence, was of an exceptional standard in terms of scientific rigour, and was expected to translate into a significant change in policy or practice.
Funding
The TRANSFUSE trial was supported by grants from the NHMRC, the Health Research Council of New Zealand, and the Irish Health Research Board, and by funding from the Australian Red Cross Blood Service.
Results Publication
Cooper DJ, McQuilten ZK, Nichol A, Ady B, Aubron C, Bailey M, Bellomo R, Gantner D, Irving DO, Kaukonen KM, McArthur C, Murray L, Pettilä V, French C; TRANSFUSE Investigators and the Australian and New Zealand Intensive Care Society Clinical Trials Group. Age of Red Cells for Transfusion and Outcomes in Critically Ill Adults. N Engl J Med. 2017 Nov 9;377(19):1858-1867. doi: 10.1056/NEJMoa1707572. Epub 2017 Sep 27.
Reference
CTG10-10