Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12617001645347
Ethics application status
Approved
Date submitted
30/11/2017
Date registered
19/12/2017
Date last updated
25/11/2019
Date data sharing statement initially provided
25/11/2019
Date results information initially provided
25/11/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Red blood cell transfusion, lowest haemoglobin level, and their association with mortality and length of hospital stay in surgical patients.
Scientific title
Associations of red blood cell transfusion and nadir haemoglobin with mortality and length of stay in surgical patients
Secondary ID [1] 293371 0
None
Universal Trial Number (UTN)
Trial acronym
None
Linked study record
None

Health condition
Health condition(s) or problem(s) studied:
Red blood cell transfusion 305494 0
Anaemia 305495 0
Condition category
Condition code
Blood 304746 304746 0 0
Anaemia

Intervention/exposure
Study type
Observational
Patient registry
True
Target follow-up duration
30
Target follow-up type
Days
Description of intervention(s) / exposure
1) Presence of a red blood cell transfusion. This will be measured at any time during the patient’s hospital admission. 2) Level of nadir haemoglobin (in grams per litre). This will be the pre-transfusion haemoglobin or nadir haemoglobin in those not transfused.
Intervention code [1] 299626 0
Not applicable
Comparator / control treatment
Patients not receiving a red blood cell transfusion. This will be compared across different levels of nadir haemoglobin.
Control group
Active

Outcomes
Primary outcome [1] 303963 0
30-day mortality
Timepoint [1] 303963 0
30 days from admission
Primary outcome [2] 303964 0
In-hospital mortality
Timepoint [2] 303964 0
At time of hospital discharge.
Primary outcome [3] 303966 0
Hospital length of stay (measured in days). This outcomes is assessed by collecting the admission date and the discharge date from the admissions data collected.
Timepoint [3] 303966 0
From hospital admission to discharge.
Secondary outcome [1] 340544 0
Nil
Timepoint [1] 340544 0
Nil

Eligibility
Key inclusion criteria
Adults admitted as elective or emergency cases for orthopaedic surgery, gastrointestinal surgery, vascular surgery, urology, cardiothoracic surgery, or neurosurgery to three public hospitals in Western Australia between July 2008 and June 2017.

Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Any patients transfused fresh frozen plasma, platelets, and cryoprecipitate will be excluded from the study. Also excluded are patients receiving a massive transfusion, patients transfused any blood products 90 days prior to admission, patients with a length of stay of less than 2 days (same day and overnight admissions), patients under the age of 18 years at admission, and patients with no haemoglobin results.

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Retrospective
Statistical methods / analysis
Exposure and outcome variables will initially be described by univariate and bivariate statistics, the latter using the chi-squared test for categorical variables and independent samples t-test for continuous variables. Logistic regression models will be applied to test the relationship that both red blood cell transfusion and nadir haemoglobin levels have with in-hospital mortality and 30-day mortality. A zero-truncated negative binomial regression model will be applied to the length of stay outcome. All regression models will adjust for the same potential confounders. A robust variance adjustment will be applied to the regression models to account for any potential correlation between multiple admissions for the same patient.

For this analysis we are also interested in whether the presence of a red blood cell transfusion modifies the effect of nadir haemoglobin on in-hospital mortality, 30-day mortality and length of stay. To test any effect modification on outcome an interaction term between nadir haemoglobin level and red blood cell transfusion will be added to the multivariable logistic regression models. Only significant interactions (defined as p-values <0.05) will be reported, with calculated odds ratios for interaction terms presented.
In addition, Kaplan-Meier curves and Cox proportional hazards models will be plotted to show time to death in patients transfused red blood cells when compared to patients not transfused red blood cells across the various nadir haemoglobin levels.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
21/12/2017
Actual
12/02/2018
Date of last participant enrolment
Anticipated
21/12/2017
Actual
12/02/2018
Date of last data collection
Anticipated
21/12/2017
Actual
12/02/2018
Sample size
Target
60000
Accrual to date
Final
60955
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 9399 0
Fiona Stanley Hospital - Murdoch
Recruitment hospital [2] 9400 0
Royal Perth Hospital - Perth
Recruitment hospital [3] 9401 0
Fremantle Hospital and Health Service - Fremantle
Recruitment postcode(s) [1] 18099 0
6150 - Murdoch
Recruitment postcode(s) [2] 18100 0
6000 - Perth
Recruitment postcode(s) [3] 18101 0
6160 - Fremantle

Funding & Sponsors
Funding source category [1] 298253 0
Hospital
Name [1] 298253 0
Royal Perth Hospital
Country [1] 298253 0
Australia
Funding source category [2] 298264 0
University
Name [2] 298264 0
University of Western Australia
Country [2] 298264 0
Australia
Primary sponsor type
Hospital
Name
Royal Perth Hospital
Address
197 Wellington St, Perth WA 6000
Country
Australia
Secondary sponsor category [1] 297060 0
None
Name [1] 297060 0
Address [1] 297060 0
Country [1] 297060 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299033 0
Royal Perth Hospital Human Research Ethics Committee
Ethics committee address [1] 299033 0
197 Wellington St, Perth WA 6000
Ethics committee country [1] 299033 0
Australia
Date submitted for ethics approval [1] 299033 0
11/10/2017
Approval date [1] 299033 0
10/11/2017
Ethics approval number [1] 299033 0
RGS0000000415

Summary
Brief summary
Anaemia, a global public health problem, is common in developing and developed countries, particularly among hospitalized patients. The World Health Organization defines anaemia as a haemoglobin concentration below 130 grams per litre in males and 120 grams in litre in females. A recent systematic review and meta-analysis on preoperative anaemia and outcomes after cardiac and non-cardiac surgery reported 39% of patients were admitted anaemic. These anaemic patients had three-fold higher odds of mortality, four-fold higher odds of acute kidney injury and twice the odds of infection. Not surprisingly, anaemia was also associated with increased transfusion, with anaemic patients five-times more likely to receive a red blood cell transfusion.

As these results indicate, red blood cell transfusions are often administered to correct low haemoglobin levels. However, correcting anaemia with transfusion is problematic as red blood cell transfusion has a dose-dependent association with increased mortality, morbidity, hospital and ICU length of stay, readmissions, and cost. Large risk-adjusted observational studies demonstrate that even transfusing a single unit of red blood cells is associated with increased adverse outcomes in surgical patients, thus recommending caution before transfusing.

In an attempt to find the “optimal” transfusion threshold, many randomized controlled trials have investigated the difference between using restrictive pre-transfusion haemoglobin thresholds compared with liberal thresholds. A restrictive strategy refers to a policy of administering red blood cell transfusions at comparatively lower pre-defined haemoglobin levels, with the goal of minimizing the use of blood. Though not always the case, restrictive transfusion thresholds are often defined as haemoglobin levels between 70 grams per litre and 80 grams per litre and liberal transfusion thresholds are commonly defined as haemoglobin levels between 90 grams per litre and 100 grams per litre.

A recent systematic review and meta-analysis published in the Cochrane Library concluded there is no difference in morbidity or mortality between restrictive and liberal transfusion strategies. However, these trials are often confounded by transfusions administered pre-randomization, a lack of comparable transfusion dosing regimens between studies, and at times small differences in actual mean pre-transfusion haemoglobin levels between control and intervention arms. In addition, these randomized controlled trials do not address transfusion efficacy and still leave many important questions unanswered. For example, whether haemoglobin thresholds lower than 70 grams per litre are just as effective as haemoglobin levels higher than 70 grams per litre. Some have suggested lower haemoglobin thresholds may be just as effective. The aim of this study is to determine what effect red blood cell transfusion has on mortality and length of stay at various levels of nadir haemoglobin.
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 2234 2234 0 0
/AnzctrAttachments/374000-Research Protocol.pdf (Protocol)

Contacts
Principal investigator
Name 79058 0
Mr Kevin Trentino
Address 79058 0
Royal Perth Hospital,
197 Wellington St, Perth WA 6000
Country 79058 0
Australia
Phone 79058 0
+61 8 6477 5110
Fax 79058 0
Email 79058 0
[email protected]
Contact person for public queries
Name 79059 0
Prof Michael Leahy
Address 79059 0
Royal Perth Hospital,
197 Wellington St, Perth WA 6000
Country 79059 0
Australia
Phone 79059 0
+61 8 9224 2405
Fax 79059 0
Email 79059 0
[email protected]
Contact person for scientific queries
Name 79060 0
Mr Kevin Trentino
Address 79060 0
Royal Perth Hospital,
197 Wellington St, Perth WA 6000
Country 79060 0
Australia
Phone 79060 0
+61 8 6477 5110
Fax 79060 0
Email 79060 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Study results articleYes Trentino KM, Leahy MF, Sanfilippo FM, Farmer SL, H... [More Details]

Documents added automatically
No additional documents have been identified.