Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12619001632189
Ethics application status
Approved
Date submitted
22/10/2019
Date registered
25/11/2019
Date last updated
28/07/2024
Date data sharing statement initially provided
25/11/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
ErythroPOietin Alfa to Prevent Mortality and Reduce Severe Disability in Critically Ill TRAUMA Patients (EPO-TRAUMA)
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 40,000IU subcutaneously administered within 24 hours of injury. Additional dose of study a drug administered on 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
Sodium chloride (0.9% Saline) subcutaneously administered within 24 hours of injury. Additional dose administered on Day 8 if none of the withholding criteria are met.
Control group
Placebo

Outcomes
Primary outcome [1] 321754 0
Combination of Mortality and Severe Disability (defined as a WHODAS 2.0 score greater or equal to 25% at six months
Timepoint [1] 321754 0
Six months
Secondary outcome [1] 376124 0
Mortality
Timepoint [1] 376124 0
Hospital Discharge

Eligibility
Key inclusion criteria
a) Are greater or equal to 18 to less than or equal 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 informed consent from a legal surrogate according to local law
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
a) GCS = 3 and fixed dilated pupils
b) Recent history of DVT, PE or other thromboembolic event (within previous 12 months or receiving concomitant anticoagulant treatment for this indication)
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
Recruiting
Date of first participant enrolment
Anticipated
1/10/2020
Actual
25/11/2020
Date of last participant enrolment
Anticipated
31/12/2025
Actual
Date of last data collection
Anticipated
30/06/2026
Actual
Sample size
Target
2500
Accrual to date
662
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,WA,VIC
Recruitment hospital [1] 18963 0
The Alfred - Melbourne
Recruitment hospital [2] 18964 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [3] 18965 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [4] 18966 0
St Vincents Private Hospital Lismore - Lismore
Recruitment hospital [5] 18967 0
John Hunter Hospital - New Lambton
Recruitment hospital [6] 18968 0
Westmead Hospital - Westmead
Recruitment hospital [7] 18969 0
St George Hospital - Kogarah
Recruitment hospital [8] 18971 0
Gold Coast University Hospital - Southport
Recruitment hospital [9] 18973 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [10] 18974 0
Royal Brisbane & Womens Hospital - Herston
Recruitment hospital [11] 21787 0
Liverpool Hospital - Liverpool
Recruitment hospital [12] 21788 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [13] 21790 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [14] 21791 0
Royal Perth Hospital - Perth
Recruitment hospital [15] 25339 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst
Recruitment postcode(s) [1] 33470 0
3004 - Melbourne
Recruitment postcode(s) [2] 33471 0
3050 - Parkville
Recruitment postcode(s) [3] 33472 0
2050 - Camperdown
Recruitment postcode(s) [4] 33473 0
2480 - Lismore
Recruitment postcode(s) [5] 33474 0
2305 - New Lambton
Recruitment postcode(s) [6] 33475 0
2145 - Westmead
Recruitment postcode(s) [7] 33476 0
2217 - Kogarah
Recruitment postcode(s) [8] 33478 0
4215 - Southport
Recruitment postcode(s) [9] 33480 0
4102 - Woolloongabba
Recruitment postcode(s) [10] 33481 0
4029 - Herston
Recruitment postcode(s) [11] 36844 0
2170 - Liverpool
Recruitment postcode(s) [12] 36845 0
2065 - St Leonards
Recruitment postcode(s) [13] 36847 0
5000 - Adelaide
Recruitment postcode(s) [14] 36848 0
6000 - Perth
Recruitment postcode(s) [15] 41044 0
2010 - Darlinghurst
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
Country [4] 23552 0
Slovenia
State/province [4] 23552 0
Country [5] 23553 0
Saudi Arabia
State/province [5] 23553 0
Country [6] 24593 0
Switzerland
State/province [6] 24593 0
Bern
Country [7] 24594 0
Germany
State/province [7] 24594 0
Berlin
Country [8] 24596 0
France
State/province [8] 24596 0
Country [9] 26478 0
Norway
State/province [9] 26478 0
Oslo
Country [10] 26479 0
Belgium
State/province [10] 26479 0
Brussels

Funding & Sponsors
Funding source category [1] 304089 0
Government body
Name [1] 304089 0
Medical Research Future Fund c/o NHMRC
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
Other Collaborative groups
Name [1] 304296 0
Irish Critical Care Clinical Trials Network
Address [1] 304296 0
University College Dublin Clinical Research centre
St. Vincent’s University Hospital, Elm Park, Dublin 4, Ireland
Country [1] 304296 0
Ireland
Secondary sponsor category [2] 308918 0
Other Collaborative groups
Name [2] 308918 0
Medical Research Institute of New Zealand
Address [2] 308918 0
7 CSB Building Wellington Hospital, Riddiford Street, Newtown, Wellington 6021, New Zealand
Country [2] 308918 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 304578 0
Melbourne Health Human Research Ethics Committee
Ethics committee address [1] 304578 0
Ethics committee country [1] 304578 0
Australia
Date submitted for ethics approval [1] 304578 0
22/11/2019
Approval date [1] 304578 0
24/02/2020
Ethics approval number [1] 304578 0

Summary
Brief summary
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
[email protected]
Contact person for public queries
Name 97455 0
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
[email protected]
Contact person for scientific queries
Name 97456 0
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
[email protected]

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 anonymised 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. [email protected]


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.