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Fresher Red Blood Cell Use In Intensive Care
(TRANSFUSE) – A Randomised Controlled Trial
Noosa
March 2012
Collaboration
ANZ – Transfusion medicine
Background
Blood transfusion associated with increased risk of death in
critically unwell patients
Marik, CCM 2008
Background
Association between age of blood and complications
Storage lesion may occur as early as 7 days and established by 14 to 21 days (Berezina J Surg Res 2002, Laczko Transfusion 1979) decreased deformability, increased adhesion and aggregation
Retrospective studies show associations between prolonged storage of red blood cells and adverse clinical outcomes Post op pneumonia: cardiothoracic (Vamvakas Transfusion 1999)
Sepsis: ICU (Purdy Can J Anaesth 1997) Increased infection: trauma (Offner Arch Surg 2002, Keller J Trauma
2002)
Prospective TBI study comparing red cells older than 19 days to freshest
no increase in cerebral oxygenation with older blood (Leal‐Noval CCM
2008)
Background
Background
Association between age of blood and complications:
A retrospective study in 6,002 cardiac surgery patients
Koch, NEJM 2008
Background
CTG & ANZIC-RC Blood research program
2008 observational study
– ICU patients; 47 sites ANZ
2008 blood bank fridge study and survey
– Age of RBCs in current practice
2010 Pilot RCT comparing freshest available vs
standard issue RBCs (2 sites)
Background
Australian and New Zealand prospective observational study
(47 ICUs, 747 patients)
Pettilä et al. Critical Care 2011,15:R116
Background
Pilot RCT results
Transfusion and RBC units’ characteristics
Characteristics
Fresher blood
group (n=25)
Standard care
group (n=26)
P
Value
12.1 ± 3.8
23 ± 8.4
<0.001
Maximum age, days
15 ± 6.5
26 ± 9.2
<0.001
Minimum age, days
9.5 ± 4.5
20.5 ± 8.9
<0.001
RBC units per patient
3.2 ± 2.6
3.8 ± 3.6
ns
Patients transfused before ICU
5 (20%)
5 (19%)
ns
Patients transfused after ICU
5 (20%)
4 (15%)
ns
Age of RBC units, days
Background
Pilot RCT results
Transfusion and RBC units’ characteristics
Characteristics
Fresher blood
group (n=25)
Standard care
group (n=26)
P
Value
12.1 ± 3.8
23 ± 8.4
<0.001
Maximum age, days
15 ± 6.5
26 ± 9.2
<0.001
Minimum age, days
9.5 ± 4.5
20.5 ± 8.9
<0.001
RBC units per patient
3.2 ± 2.6
3.8 ± 3.6
ns
Patients transfused before ICU
5 (20%)
5 (19%)
ns
Patients transfused after ICU
5 (20%)
4 (15%)
ns
Age of RBC units, days
Background
Pilot RCT results
Transfusion and RBC units’ characteristics
Characteristics
Fresher blood
group (n=25)
Standard care
group (n=26)
P
Value
12.1 ± 3.8
23 ± 8.4
<0.001
Maximum age, days
15 ± 6.5
26 ± 9.2
<0.001
Minimum age, days
9.5 ± 4.5
20.5 ± 8.9
<0.001
RBC units per patient
3.2 ± 2.6
3.8 ± 3.6
ns
Patients transfused before ICU
5 (20%)
5 (19%)
ns
Patients transfused after ICU
5 (20%)
4 (15%)
ns
Age of RBC units, days
Background
Pilot RCT results
Transfusion and RBC units’ characteristics
Characteristics
Fresher blood
group (n=25)
Standard care
group (n=26)
P
Value
12.1 ± 3.8
23 ± 8.4
<0.001
Maximum age, days
15 ± 6.5
26 ± 9.2
<0.001
Minimum age, days
9.5 ± 4.5
20.5 ± 8.9
<0.001
RBC units per patient
3.2 ± 2.6
3.8 ± 3.6
ns
Patients transfused before ICU
5 (20%)
5 (19%)
ns
Patients transfused after ICU
5 (20%)
4 (15%)
ns
Age of RBC units, days
Background
Ongoing international studies
RECESS
(n=1,400) cardiac surgery
patients
RBC ≤ 10 days old vs ≥ 21
days
Low baseline mortality hence
surrogate outcome
measures
Not generalisable to
heterogeneous ICU
population
ABLE
(n=2,500)
RBC ≤ 7 days old vs
standard issue
Pragmatically unrealistic,
likely underpowered
Hypothesis
Aim of the TRANSFUSE-RCT
To determine whether transfusion of freshest available
RBC compared to standard care improves patient
survival (90 days mortality) in ICU patients
Randomised, controlled, double blinded, multicentre trial
Methods
Inclusion criteria
1. ICU patient with anticipated stay ≥ 24 hours requiring RBC
transfusion
Methods
1.
2.
3.
4.
5.
6.
Exclusion criteria
Anticipated length of ICU stay <24hrs
Previous RBC transfusion (current hospital admission)
Pregnancy
Cardiac surgery (current hospital admission)
Haematological disease or transplantation
Patient has known objection to administration of blood
products
7. Patient is moribund (estimated survival <24hrs)
8. Not in patients best interest – treating physicians decision
Methods
Methods
Study procedures
1. Screening of eligible ICU patients (ICU)
2. Web based randomisation (ICU) = study number
3. ICU convey study number to transfusion service by phone when
ordering RBC transfusion & on the request slip
4. Transfusion service scientist checks study number on randomisation
schedule
5. Scientist allocates either freshest available RBC or standard care
(based on study number)
6. ICU team in charge of patient is blind while transfusion service is not
blind
7. ICU collect study data & follow up patient at 90 days
Timeline
Timeline
Jan/Feb 2012 – expressions of interest
March 2012 – Alfred HREC
April – Oct 2012 – ANZ HREC approvals
Oct 2012 – Mar 2015 – recruitment
July 2015 – complete follow up
Aug 2015 – database lock
Nov 2015 – submit for publication
Budget
Payment and Recruitment Plan
$500 per patient to ICU
$50 per patient to transfusion service
Planned enrolment: 5,000 patients
Planned sites: 50 in Australia and New Zealand
Budget
Funding
Budget - $3,896,267
NHMRC granted - $2,761,870 (75%)
NBA requested - $600,000
ARCBS – supported in principle
NZ HRC – application in progress
Thank you