Standard Issue Transfusion Versus Fresher Red Blood Cell Use in Intensive Care- A Randomised Controlled Trial (TRANSFUSE)

A Multi-centre Randomised Double Blinded Phase III Trial of the Effect of Standard Issue Red Blood Cell Blood Units on Mortality Compared to Freshest Available Red Blood Cell Units

In Australia, blood for transfusion has a "use by" date of 42 days after collection. The actual age of blood given to patients depends on what is available at the time and the rate of usage. During the last decade, it has been reported that blood transfusion in patients admitted to intensive care was associated with an independent increase of mortality. Some research suggests that transfusion of fresher blood might help patients in the intensive care unit to reach a better recovery. This project will test whether patients who receive 'fresher' blood do better than patients who receive 'standard issue' blood.

Study Overview

• Status: Completed
• Conditions: Transfusion; Age of Blood
• Intervention / Treatment: Other: Blood transfusion

Detailed Description

Inclusion criteria

•Patients hospitalised in ICU with an anticipated ICU stay of at least 24 hours, in whom the decision has been made by medical staff to transfuse at least one RBC unit.

Exclusion criteria

• Age younger than 18
• Previous RBC transfusion during the current hospital admission (including transfusion in another hospital for transferred patients)
• Diagnosis of transplantation or hematologic diseases
• Pregnancy
• Cardiac surgery during the present hospital admission
• Expected to die imminently (<24hrs)
• The treating physician believes it is not in the best interest of the patient to be randomised in this trial.
• Known objection to the administration of human blood products
• Participation in a competing study

Primary outcome- 90 day mortality

Secondary outcomes

1. 28 day mortality
2. Persistent Organ Dysfunction combined with death at 28
3. Days alive and free of mechanical ventilation at day 90 post randomisation
4. Day alive and free of renal replacement therapy at day 90 post randomisation
5. Blood stream infection in ICU (post randomisation) defined using the Center for Disease Control and Prevention/National Healthcare Safety Network criteria
6. Length of stay in ICU and in hospital post randomisation
7. Febrile non-haemolytic transfusion reactions
8. EQ-5D score at Day 90 post randomisation

• Study Type: Interventional
• Enrollment (Actual): 4994
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Adelaide, Australia
    • Royal Adelaide Hospital
  • Adelaide, Australia
    • Lyell McEwin Hospital
  • Adelaide, Australia
    • Queen Elizabeth Hospital
  • Albury, Australia
    • Albury Hospital
  • Bendigo, Australia
    • Bendigo Hospital
  • Brisbane, Australia
    • Mater Adult Hospital
  • Brisbane, Australia
    • Princess Alexandra Hospital
  • Brisbane, Australia
    • Royal Brisbane and Women's Hospital
  • Brisbane, Australia
    • Logan Hospital
  • Brisbane, Australia
    • Mater Private Hospital
  • Canberra, Australia
    • Canberra Hospital
  • Canberra, Australia
    • Calvary Health
  • Dandenong, Australia
    • Dandenong Hospital
  • Geelong, Australia
    • Geelong Hospital
  • Gold Coast, Australia
    • Gold Coast Hospital
  • Gosford, Australia
    • Gosford Hospital
  • Heidelberg, Australia
    • Austin Hospital
  • Hobart, Australia
    • Royal Hobart Hospital
  • Melbourne, Australia
    • Monash Medical Centre
  • Melbourne, Australia
    • Royal Melbourne Hospital
  • Melbourne, Australia
    • St Vincent's Hospital
  • Melbourne, Australia
    • Cabrini Hospital
  • Melbourne, Australia
    • Frankston Hospital
  • Melbourne, Australia
    • Knox Private Hospital
  • Melbourne, Australia
    • Northern Hospital
  • Melbourne, Australia
    • Sunshine Hospital
  • Melbourne, Australia
    • Western Hospital
  • Newcastle, Australia
    • John Hunter Hospital
  • Newcastle, Australia
    • Calvary Mater Newcastle
  • Perth, Australia
    • Royal Perth Hospital
  • Perth, Australia
    • Fiona Stanley Hospital
  • Perth, Australia
    • St John of God Murdoch Hospital
  • Richmond, Australia
    • Epworth Hospital
  • Sydney, Australia
    • Royal Prince Alfred Hospital
  • Sydney, Australia
    • Nepean Hospital
  • Sydney, Australia
    • Blacktown Hospital
  • Sydney, Australia
    • Prince of Wales Hospital
  • Sydney, Australia
    • St George Hospital
  • Sydney, Australia
    • St Vincent's Hospital
  • Tamworth, Australia
    • Tamworth Hospital
  • Wollongong, Australia
    • Wollongong Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • The Alfred Hospital
• Finland
  • Helsinki, Finland
    • Helsinki University Hospital
  • Tampere, Finland
    • Tampere University Hospital
• Ireland
  • Cork, Ireland
    • Cork University Hospital
  • Dublin, Ireland
    • Beaumont Hospital
  • Dublin, Ireland
    • St James's Hospital
  • Dublin, Ireland
    • St Vincent's University Hospital
  • Galway, Ireland
    • Galway Regional Hospital
  • Limerick, Ireland
    • Limerick Regional Hospital
• New Zealand
  • Auckland, New Zealand
    • Middlemore Hospital
  • Auckland, New Zealand
    • North Shore Hospital
  • Auckland, New Zealand
    • Auckland City Hospital CVICU
  • Auckland, New Zealand
    • Auckland City Hospital DCCM
  • Christchurch, New Zealand
    • ChristChurch Hospital
  • Dunedin, New Zealand
    • Dunedin Hospital
  • Hamilton, New Zealand
    • Waikato Hospital
  • Nelson, New Zealand
    • Nelson Hospital
  • Wellington, New Zealand
    • Wellington Hospital
• Saudi Arabia
  • Riyadh, Saudi Arabia
    • King Abdulaziz Medical City

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients hospitalised in ICU with an anticipated ICU stay of at least 24 hours, in whom the decision has been made by medical staff to transfuse at least one RBC unit.

Exclusion Criteria:

• Age younger than 18
• Previous RBC transfusion during the current hospital admission (including transfusion in another hospital for transferred patients)
• Diagnosis of transplantation or hematologic diseases
• Pregnancy
• Cardiac surgery during the present hospital admission
• Expected to die imminently (<24hrs)
• The treating physician believes it is not in the best interest of the patient to be randomised in this trial.
• Known objection to the administration of human blood products
• Participation in a competing study (see below)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard of care; Blood Transfusion Standard of care- oldest blood.	Other: Blood transfusion; Blood transfusion in ICU patients aged 18 and over.
Other: Arm B; Blood Transfusion Freshest blood.	Other: Blood transfusion; Blood transfusion in ICU patients aged 18 and over.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality at Day 90	Mortality at Day 90	90 Day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality at Day 28	Mortality at day 28	28 day
Persistent Organ Dysfunction Combined With Death Measured at Day 28	Persistent Organ Dysfunction combined with death measured at day 28	day 28
Days Alive and Free of Mechanical Ventilation	Days alive and free of mechanical ventilation	day 28
Day Alive and Free of Renal Replacement Therapy.	Day alive and free of renal replacement therapy.	day 28
Blood Stream Infection in ICU (Post Randomisation)	Blood stream infection in ICU (post randomisation) Time Frame is in Days	While in ICU-Median duration in ICU - short term storage group was 4.2 days (2.0 - 9.3), long term storage group was 4.2 days (1.9 - 9.4)
Length of Stay in ICU and in Hospital Post Randomisation (Days)	Median duration in ICU - short term storage group was 4.2 (2.0 - 9.3), long term storage group was 4.2 (1.9 - 9.4) Median duration in Hospital - short term storage group was 14.5 (7.4 - 27.5), long term storage group was 14.7 (7.4 - 28.3) In Days	Median duration in ICU- short term storage group 4.2 Days (2.0 - 9.3), long term storage group 4.2 Days (1.9 - 9.4). Median duration in Hospital- short term storage group was 14.5 days (7.4 - 27.5), long term storage group was 14.7 days(7.4 - 28.3)
Proportion of Patients Who Suffer at Least One Febrile Non-haemolytic Transfusion Reaction in ICU	Proportion of patients who suffer at least one febrile non-haemolytic transfusion reaction in ICU	While in ICU-Median duration in ICU - short term storage group was 4.2 days (2.0 - 9.3), long term storage group was 4.2 days (1.9 - 9.4)
EuroQol-5Dimension 5 Level (EQ-5D-5L) Score at Day 180 Post Randomisation	EuroQol-5Dimension 5 level (EQ-5D-5L) score at day 180 post randomisation - not reported yet	Day 180

Collaborators and Investigators

• Sponsor: Australian and New Zealand Intensive Care Research Centre
• Collaborators: University College Dublin; King Abdulaziz Medical City; Australian Red Cross; New Zealand Blood Service; Irish Blood Transfusion Service; Finnish Red Cross Blood Service
• Investigators: Principal Investigator: D. James Cooper, A.O., M.D., Monash University/Alfred Hospital

Publications and helpful links

General Publications

• Cooper DJ, McQuilten ZK, Nichol A, Ady B, Aubron C, Bailey M, Bellomo R, Gantner D, Irving DO, Kaukonen KM, McArthur C, Murray L, Pettila 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. Erratum In: N Engl J Med. 2019 Aug 29;381(9):890.
• Kaukonen KM, Bailey M, Ady B, Aubron C, French C, Gantner D, Irving D, Murray L, Nichol A, Pettila V, McQuilten Z, Cooper DJ. A randomised controlled trial of standard transfusion versus fresher red blood cell use in intensive care (TRANSFUSE): protocol and statistical analysis plan. Crit Care Resusc. 2014 Dec;16(4):255-61.
• Kekre N, Mallick R, Allan D, Tinmouth A, Tay J. The impact of prolonged storage of red blood cells on cancer survival. PLoS One. 2013 Jul 16;8(7):e68820. doi: 10.1371/journal.pone.0068820. Print 2013.

Helpful Links

• Australia and New Zealand Intensive Care Research Centre

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (Actual): April 1, 2017
• Study Completion (Actual): June 1, 2017

Study Registration Dates

• First Submitted: July 9, 2012
• First Submitted That Met QC Criteria: July 10, 2012
• First Posted (Estimate): July 11, 2012

Study Record Updates

• Last Update Posted (Actual): October 22, 2020
• Last Update Submitted That Met QC Criteria: October 19, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Other Study ID Numbers: ANZICRCDJC006

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided