COVID-19 studies are our top priority. For all other trials, there is a 4-week delay in processing a trial submitted/resubmitted to the ANZCTR and additional delays for updates of registered trials. We appreciate your patience.

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
ACTRN12619001632189p
Ethics application status
Submitted, not yet approved
Date submitted
22/10/2019
Date registered
25/11/2019
Date last updated
18/02/2020
Date data sharing statement initially provided
25/11/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
A clinical trial to assess the effect of epoetin alfa (EPO) on death and severe disability in critically ill trauma patients
Scientific title
A randomised, double blind, placebo-controlled trial to determine the effect of erythropoietin alfa compared with placebo on death and severe disability in mechanically ventilated critically ill patients following traumatic injury.
Secondary ID [1] 299612 0
None
Universal Trial Number (UTN)
U1111-1242-3694
Trial acronym
EPO TRAUMA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Trauma 314902 0
Critical Illness 314903 0
Condition category
Condition code
Injuries and Accidents 313259 313259 0 0
Other injuries and accidents
Emergency medicine 313478 313478 0 0
Other emergency care

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Epoetin alfa 4000IU Subcutaneously administered within 24 hours of injury.
Additional dose of study drug on study day 8 if none of the withholding criteria are met. Study drug is withheld if the Hb concentration is greater than 120 g/L
Intervention will be in major hospitals.
Intervention code [1] 315865 0
Treatment: Drugs
Comparator / control treatment
Matching Placebo (0.9% Saline) subcutaneously
Control group
Placebo

Outcomes
Primary outcome [1] 321754 0
Composite of death and severe disability (defined as WHODAS 2.0 >24%)
Timepoint [1] 321754 0
Six months
Secondary outcome [1] 376124 0
Mortality
Timepoint [1] 376124 0
Hospital Discharge

Eligibility
Key inclusion criteria
a) Are = 18 to = 75 years of age
b) Are < 24 hours since primary traumatic injury
c) Are invasively mechanically ventilated
d) Are expected to stay in the ICU = 48 hours
e) Have a haemoglobin not exceeding the upper limit of the applicable normal (ULN) reference range in clinical use at the treating institution
f) Have written informed consent from legal surrogate according to local law
Minimum age
18 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
a) GCS = 3 and fixed dilated pupils
b) History of DVT, PE or other thromboembolic event
c) A chronic hypercoagulable disorder, including known malignancy
d) Treatment with EPO in the last 30 days
e) First dose of study drug unable to be given within 24 hours of primary injury
f) Pregnancy or lactation or 3 months post-partum
g) Expected to die imminently (< 24 hours)
h) Known sensitivity to mammalian cell derived products
i) Known contraindication to epoetin alfa
j) End stage renal failure (receives chronic dialysis)
k) Severe pre-existing physical or mental disability or severe co-morbidity that may interfere with the assessment of outcome
l) The treating physician believes it is not in the best interest of the patient to be randomised to this trial

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Central randomistion by comptuer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Web-based block randomisation stratified by site, penetrating or non penetrating injury, and severity of traumatic brain injury
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Independent senior statisticians at Monash University Department of Epidemiology and Preventive Medicine will perform data analysis on an intention-to-treat basis. Baseline and outcome variables will be compared using Chi-square tests for equal proportion, Student’s t-test for normally distributed outcomes and Wilcoxon rank-sum tests otherwise. Multivariate models adjusting for baseline imbalances and known covariates will be performed using logistic regression. A p-value of 0.05 will be considered to be statistically significant. The primary cost-effectiveness analysis will be conducted from the healthcare payer’s perspective using an analytical time frame of 6-months. We will calculate incremental cost-effectiveness ratios, including the cost per additional quality-adjusted life year (QALY) for EPO versus placebo (CIF). Hospital costs will be determined using clinical costing systems at each participating site where available. Post discharge costs will be determined from hospital records and patient or proxy interviews at 6 months post injury. A secondary analysis will determine long term cost-effectiveness through development of a decision analytic model using trial outcome data extrapolated into the future. A detailed statistical analysis plan will be published prior to completion.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,NT,QLD,SA,TAS,WA,VIC
Recruitment outside Australia
Country [1] 21952 0
Finland
State/province [1] 21952 0
Country [2] 21953 0
Ireland
State/province [2] 21953 0
Country [3] 22126 0
New Zealand
State/province [3] 22126 0

Funding & Sponsors
Funding source category [1] 304089 0
Government body
Name [1] 304089 0
Medical Research Future Fund c/o NHMRC
Address [1] 304089 0
16 Marcus Clarke Street
Canberra 2601
ACT
Country [1] 304089 0
Australia
Primary sponsor type
University
Name
Monash University
Address
Australian and New Zealand Intensive Care Research Centre
Department of Epidemiology and Preventive Medicine
School of Public Health and Preventive Medicine
Monash University
Level 3, 553 St Kilda Road
Melbourne 3004
Victoria, Australia
Country
Australia
Secondary sponsor category [1] 304296 0
None
Name [1] 304296 0
Address [1] 304296 0
Country [1] 304296 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 304578 0
Melbourne Health Human Research Ethics Committee
Ethics committee address [1] 304578 0
Royal Melbourne Hospital
Grattan Street, Carlton 3052
Victoria
Ethics committee country [1] 304578 0
Australia
Date submitted for ethics approval [1] 304578 0
22/11/2019
Approval date [1] 304578 0
Ethics approval number [1] 304578 0

Summary
Brief summary
Prior research strongly suggests that the drug epoetin alfa improves the outcome of critically ill trauma patients. If proven correct, this has important implications for the management of trauma patients throughout the world.. We will conduct an international multi-centre trial in critically ill trauma patients that will determine the effect epoetin alfa on the rate of death and severe disability.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 97454 0
A/Prof Craig French
Address 97454 0
Western Health
160 Gordon Street,
Footscray 3011
Victoria
Country 97454 0
Australia
Phone 97454 0
+61 03 8345 6639
Fax 97454 0
Email 97454 0
craig.french@wh.org.au
Contact person for public queries
Name 97455 0
Ms Vicki Papanikolaou
Address 97455 0
Australian and New Zealand Intensive Care Research Centre
Department of Epidemiology and Preventive Medicine
School of Public Health and Preventive Medicine
Monash University
Level 3, 553 St Kilda Road
Melbourne 3004
Victoria, Australia
Country 97455 0
Australia
Phone 97455 0
+61 03 9905 6645
Fax 97455 0
Email 97455 0
vicki.papanikolaou@monash.edu
Contact person for scientific queries
Name 97456 0
A/Prof Craig French
Address 97456 0
Western Health
160 Gordon Street,
Footscray 3011
Victoria
Country 97456 0
Australia
Phone 97456 0
+61 03 8345 6639
Fax 97456 0
Email 97456 0
craig.french@wh.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
All de-identified individual patient data as per the data sharing policy of the ANZIC-RC, Monash University
When will data be available (start and end dates)?
Two years after publication of the primary manuscript. No end date.
Available to whom?
Researchers who provide a methodically sound scientific proposal as per data sharing policy of the ANZIC-RC, Monash University
Available for what types of analyses?
Only to achieve the aims of the approved proposal
How or where can data be obtained?
Access subject to approval by the Australian and New Zealand Intensive Care Research Centre. anzicrc@monash.edu
What supporting documents are/will be available?
No other documents available
Summary results
No Results