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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 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]

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

Anaemia

Condition category

Condition code

Blood

Anaemia

Intervention/exposure

Study type

Observational

Patient registry

True

Target follow-up duration

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]

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]

30-day mortality

Timepoint [1]

30 days from admission

Primary outcome [2]

In-hospital mortality

Timepoint [2]

At time of hospital discharge.

Primary outcome [3]

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]

From hospital admission to discharge.

Secondary outcome [1]

Nil

Timepoint [1]

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?

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)

Recruitment hospital [1]

Fiona Stanley Hospital - Murdoch

Recruitment hospital [2]

Royal Perth Hospital - Perth

Recruitment hospital [3]

Fremantle Hospital and Health Service - Fremantle

Recruitment postcode(s) [1]

6150 - Murdoch

Recruitment postcode(s) [2]

6000 - Perth

Recruitment postcode(s) [3]

6160 - Fremantle

Funding & Sponsors

Funding source category [1]

Hospital

Name [1]

Royal Perth Hospital

Address [1]

197 Wellington St, Perth WA 6000

Country [1]

Australia

Funding source category [2]

University

Name [2]

University of Western Australia

Address [2]

35 Stirling Hwy, Crawley WA 6009

Country [2]

Australia

Primary sponsor type

Hospital

Name

Royal Perth Hospital

Address

197 Wellington St, Perth WA 6000

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Royal Perth Hospital Human Research Ethics Committee

Ethics committee address [1]

197 Wellington St, Perth WA 6000

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

11/10/2017

Approval date [1]

10/11/2017

Ethics approval number [1]

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]

/AnzctrAttachments/374000-Research Protocol.pdf (Protocol)

Contacts

Principal investigator

Name

Mr Kevin Trentino

Address

Royal Perth Hospital,
197 Wellington St, Perth WA 6000

Country

Australia

Phone

+61 8 6477 5110

Fax

[email protected]

Contact person for public queries

Name

Michael Leahy

Address

Royal Perth Hospital,
197 Wellington St, Perth WA 6000

Country

Australia

Phone

+61 8 9224 2405

Fax

[email protected]

Contact person for scientific queries

Name

Kevin Trentino

Address

Royal Perth Hospital,
197 Wellington St, Perth WA 6000

Country

Australia

Phone

+61 8 6477 5110

Fax

[email protected]

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

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

No documents have been uploaded by study researchers.

Documents added automatically

No additional documents have been identified.

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