TraumaPhase 3EPO-TRAUMANCT04588311
ErythroPOietin Alfa to Prevent Mortality and Reduce Severe Disability in Critically Ill TRAUMA Patients
A Phase 3 study testing Epoetin Alfa 40000 UNT/ML and Sodium Chloride 0.9% in people with Trauma and Traumatic Injury, run by Australian and New Zealand Intensive Care Research Centre at 41 sites in 9 countries.
Trial summary
The EPO-TRAUMA study is a prospective, multi-centre, double-blind, phase III, randomised controlled trial evaluating the efficacy of epoetin alfa compared to placebo in reducing mortality and severe disability at six months in critically ill trauma patients. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Trauma, Traumatic Injury, Traumatic Brain Injury
- What is being tested?
- Epoetin Alfa 40000 UNT/ML and Sodium Chloride 0.9%
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 2,500 participants
- Where
- 41 sitesin 9 countries
- Study dates
- 9 Nov 2020to 31 Aug 2027
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Inclusion Criteria: Patients with trauma admitted to the ICU who:
- Are ≥ 18 to ≤ 75 years of age
- Are < 24 hours since primary traumatic injury
- Are invasively mechanically ventilated
- Are expected to stay in the ICU ≥ 48 hours
- Have a haemoglobin not exceeding the upper limit of the applicable normal (ULN) reference range in clinical use at the treating institution
- Have informed consent from a legal surrogate according to local law
Exclusion Criteria: Patients will be excluded from the study if any of the following criteria apply:
- GCS = 3 and fixed dilated pupils
- Recent history of DVT, PE or other thromboembolic event (within previous 12 months or receiving concomitant anticoagulant treatment for this indication)
- A chronic hypercoagulable disorder, including known malignancy
- Treatment with EPO in the last 30 days
- First dose of study drug unable to be given within 24 hours of primary injury
- Pregnancy or lactation or 3 months postpartum
- Expected to die imminently (< 24 hours)
- Known sensitivity to mammalian cell derived products
- Known contraindication to epoetin alfa
- End stage renal failure (receives chronic dialysis)
- Severe pre-existing physical or mental disability or severe co-morbidity that may interfere with the assessment of outcome
- The treating physician believes it is not in the best interest of the patient to be randomised to this trial
Trial locations and contacts
41 sites in 9 countries. Contact the study team or a site near you to ask about taking part.
41 sites in 9 countries
Australia17 sites, 15 recruiting
- Recruiting
Royal Adelaide Hospital
Adelaide, South Australia, 5000
Mark Plummer
- Not yet recruiting
Flinders Medical Centre
Adelaide, South Australia, 5042
Dr Dieter Linde, dieter.linde@sa.gov.au
- Withdrawn
Cairns Hospital
Cairns, Queensland, 4870
- Recruiting
Royal Prince Alfred Hospital
Camperdown, New South Wales, 2050
David Gattas
- Active, not recruiting
St Vincent's Hospital Sydney
Darlinghurst, New South Wales, 2010
- Recruiting
Royal Brisbane and Women's Hospital
Herston, Queensland, 4029
Michael Reade
- Recruiting
St George Hospital
Kogarah, New South Wales, 2217
Kush Deshpande
- Recruiting
Liverpool Hospital
Liverpool, New South Wales, 2170
Avinash Sharma
- Recruiting
The Alfred Hospital
Melbourne, Victoria, 3004
Dashiell Gantner
- Recruiting
Royal Melbourne Hospital
Melbourne, Victoria, 3050
Yasmine Ali Abdelhamid
- Recruiting
John Hunter Hospital
New Lambton Heights, New South Wales, 2305
Zsolt Balogh
- Recruiting
Royal Perth Hospital
Perth, Western Australia, 6000
Robert McNamara
- Recruiting
Royal North Shore Hospital
Saint Leonards, New South Wales, 2065
Chris Andersen
- Recruiting
Gold Coast University Hospital
Southport, Queensland, 4215
Don Campbell
- Not yet recruiting
Royal Darwin Hospital
Tiwi, Northern Territory, 0810
Lewis Campbell
- Recruiting
Westmead Hospital
Westmead, New South Wales, 2145
Vineet Nayyar
- Recruiting
Princess Alexandra Hospital
Woolloongabba, Queensland, 4102
Adam Suliman
Belgium6 sites, 6 recruiting
- Not yet recruiting
Cliniques Universitaires Saint-Luc
Brussels
- Not yet recruiting
HUB Hopital Erasme
Brussels
- Recruiting
CHU-Charleroi Chimay
Charleroi
Prof Michael Piagnerelli
- Not yet recruiting
Ziekenhuis Oost-Limburg
Genk
- Not yet recruiting
Ghent University Hospital
Ghent
- Not yet recruiting
CHR de la Citadelle de LIEGE
Liège
New Zealand5 sites, 5 recruiting
- Recruiting
Middlemore Hospital
Auckland, Otahuhu, 1640
Tony Williams
- Recruiting
Christchurch Hospital
Christchurch, Christchurch, 8011
Brandon Burke
- Recruiting
Auckland City Hospital
Grafton, Auckland, 1023
Colin McArthur
- Recruiting
Waikato Hospital
Hamilton, Waikato Region, 3204
Robert Martynoga
- Recruiting
Wellington Hospital
Newtown, Wellington Region, 6021
James Moore
Finland3 sites, 3 recruiting
- Recruiting
Helsinki University Hospital (HUS)
Helsinki
Markus Skrifvars
- Recruiting
Kuopio University Hospital
Kuopio
Stepani Bendel
- Recruiting
Turku University Hospital
Turku
Timo Laitio
Ireland3 sites, 3 recruiting
- Recruiting
Beaumont Hospital
Beaumont
Gerard Curley
- Recruiting
Cork University Hospital
Cork
Patrick Seigne
- Recruiting
St Vincent's University Hospital
Dublin
Switzerland3 sites, 3 recruiting
- Recruiting
University Hospital Bern
Bern
Matthias Hänggi
- Not yet recruiting
Lucerne Cantonal Hospital
Lucerne
Andreas Bloch
- Recruiting
St. Gallen Cantonal Hospital
Sankt Gallen
Urs Pietsch
Slovenia2 sites, 2 recruiting
- Recruiting
University Medical Centre Ljubljana
Ljubljana
Anja Kramaric
Primoz Gradisek
- Recruiting
University Medical Centre Maribor
Maribor
Andreja M Petrun
Germany1 site, 1 recruiting
- Recruiting
University Hospital Münster
Münster
Alexander Zarbock
Saudi Arabia1 site, 1 recruiting
- Recruiting
King Abdulaziz Medical City
Riyadh
Hassan Alhabeeb
About this study
Official title: A Randomised, Double-blind, Placebo-controlled Trial of Erythropoietin Alfa Versus Placebo in Mechanically Ventilated Critically Ill Patients Following Traumatic Injury
The EPO-TRAUMA study is a prospective, multi-centre, double-blind, phase III, randomised controlled trial evaluating the efficacy of epoetin alfa compared to placebo in reducing mortality and severe disability at six months in critically ill trauma patients.
2500 mechanically ventilated ICU patients admitted with a primary trauma diagnosis presenting to the ICU will be recruited into the study from participating study centres in Australia, New Zealand, Europe, and Saudi Arabia.
Read the detailed description
Trauma can cause many injuries, some of which are life-threatening and require treatment in an intensive care unit (ICU). Despite best available treatment and therapies, people who sustain a critical traumatic injury are at greater risk of death or long-term disability. From 2010 to 2015, approximately 9% of people admitted to an ICU in Australia and New Zealand for treatment of their injuries, did not survive. In Victoria, 6-months post injury, approximately 31% of people who were critically injured developed severe disabilities or died.
Following a traumatic injury, a number of complex pathways are activated by the body. These pathways can occur over hours or weeks and may lead to damage of cells, tissues or blood vessels and may destroy other healthy tissue. The treatment of traumatic injury focuses on trying to minimise further damage that can occur after the initial injury.
Erythropoietin is a glycoprotein hormone essential for erythropoiesis and was first purified in 1977. Its human recombinant analogues known as erythropoiesis stimulating agents (ESAs) are approved for human therapeutic use. However, erythropoietin is also a pleiotropic cytokine with effects beyond just erythropoiesis. Studies in animals have demonstrated the potential protective effects of erythropoietin to organs including the brain, kidney, liver and heart, and anti-inflammatory properties.
Previous research suggests the use of the ESA called epoetin alfa, increases the number of patients surviving severe trauma and reduces the risk of disability in those who survive.
The primary aim of the study is to determine the efficacy of epoetin alfa compared to placebo in reducing mortality and severe disability at six months in critically ill trauma patients.
2500 mechanically ventilated ICU patients admitted with a primary trauma diagnosis presenting to the ICU will be recruited into the study from participating study centres in Australia, New Zealand, Europe, and Saudi Arabia.
- Conditions
- Trauma, Traumatic Injury, Traumatic Brain Injury, Wounds and Injuries, Penetrating Injury, Blunt Injury
- Being tested
- Epoetin Alfa 40000 UNT/ML, Sodium Chloride 0.9%
- Keywords
- Intensive Care Unit, Trauma, Major trauma, Traumatic injury, EPO, Erythropoietin, Epoetin alfa
- Medical subject headings
- Wounds and Injuries, Brain Injuries, Traumatic, Wounds, Penetrating, Wounds, Nonpenetrating, Multiple Trauma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Epoetin Alfa 40000 UNT/MLDrug
Also called Eprex, Binocrit
Epoetin alfa 40,000IU 1mL pre-filled syringe given as subcutaneous injection.
Sodium Chloride 0.9%Drug
Also called Placebo, Saline
Sodium Chloride 0.9% 1mL in volume given as subcutaneous injection.
| Study group | Role | What they receive |
|---|---|---|
| Erythropoietin (EPO) | Active comparator | Epoetin alfa 40,000 IU (1mL pre-filled syringe) will be given by subcutaneous injection to eligible patients on Study Days 1 and 8 during the intensive care unit stay. Receives: Drug: Epoetin Alfa 40000 UNT/ML |
| Placebo | Placebo comparator | Sodium Chloride 0.9% (1mL in volume) will be given by subcutaneous injection to eligible patients allocated to the placebo arm on Study Days 1 and 8 during the intensive care unit stay. Receives: Drug: Sodium Chloride 0.9% |
What is being measured
The primary outcome is the main question the study is designed to answer.
Combined proportion of participants who have died or have severe disability (WHODAS 2.0 > 25)
Measured: 6-months
Secondary outcomes (6)
Mortality at 6-months
Measured: 6 months
Mortality at ICU discharge
Measured: 6-months
Mortality at Hospital discharge
Measured: 6-months
Mortality at day 28
Measured: 28 days
Proportion of participants with a favourable Glasgow Outcome Score Extended (GOSE) (GOSE 5-8) compared to those have have died (GOSE 1), or have severe disability (GOSE 2-4).
Measured: 6-months
Proportion of participants with composite thrombotic vascular events (deep vein thrombosis (DVT), pulmonary embolism (PE), myocardial infarction (PI), cardiac arrest and cerebrovascular events) at 6 months.
Measured: 6-months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Oct 2020
- Study start9 Nov 2020
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Aug 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for TraumaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 2,500 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Australian and New Zealand Intensive Care Research Centre
- Sponsor type
- University, hospital or other
- Collaborators
- University College Dublin, Medical Research Institute of New Zealand, Medical Research Future Fund, Health Research Board, Ireland, Health Research Council, New Zealand, Irish Critical Care Clinical Trials Network, ANZICS Clinical Trials Group, Monash University
- Responsible party
- Sponsor
- Investigators
- Associate Professor Craig French, Study chair, Western Health; ANZIC Research CentreProfessor Alistair Nichol, Study chair, University College Dublin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04588311
- Sponsor's protocol ID
- ANZIC-RC/CF001
- Other IDs
- U1111-1242-3694, 2020-003388-24
- Acronym
- EPO-TRAUMA
- Status last verified
- Jul 2025
- First submitted
- 1 Oct 2020
- Last updated
- 16 Jul 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: At the conclusion of the study, the study management committee will consider requests from researchers who provide a methodically sound scientific proposal as per the Data Sharing Policy set out in the ANZIC-RC Terms of Reference.
Publications
Nichol A, French C, Little L, Haddad S, Presneill J, Arabi Y, Bailey M, Cooper DJ, Duranteau J, Huet O, Mak A, McArthur C, Pettila V, Skrifvars M, Vallance S, Varma D, Wills J, Bellomo R; EPO-TBI Investigators; ANZICS Clinical Trials Group. Erythropoietin in traumatic brain injury (EPO-TBI): a double-blind randomised controlled trial. Lancet. 2015 Dec 19;386(10012):2499-506. doi: 10.1016/S0140-6736(15)00386-4. Epub 2015 Oct 6.
PubMed 26452709
Study at a glance
From the registry record, last updated by the sponsor on 16 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised, Double-blind, Placebo-controlled Trial of Erythropoietin Alfa Versus Placebo in Mechanically Ventilated Critically Ill Patients Following Traumatic Injury
- ClinicalTrials.gov ID
- NCT04588311
- Acronym / sponsor ID
- EPO-TRAUMA / ANZIC-RC/CF001
- Conditions
- Trauma, Traumatic Injury, Traumatic Brain Injury, Wounds and Injuries, Penetrating Injury, Blunt Injury
- Keywords
- Intensive Care Unit, Trauma, Major trauma, Traumatic injury, EPO, Erythropoietin, Epoetin alfa
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 2,500 participants (estimated)
- Lead sponsor
- Australian and New Zealand Intensive Care Research CentreUniversity, hospital or other
- Collaborators
- University College Dublin, Medical Research Institute of New Zealand, Medical Research Future Fund, Health Research Board, Ireland, Health Research Council, New Zealand, Irish Critical Care Clinical Trials Network, ANZICS Clinical Trials Group, Monash University
- Study start
- 9 Nov 2020 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Aug 2027 (estimated)
- First posted
- 19 Oct 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The EPO-TRAUMA study is a prospective, multi-centre, double-blind, phase III, randomised controlled trial evaluating the efficacy of epoetin alfa compared to placebo in reducing mortality and severe disability at six months in critically ill trauma patients.
2500 mechanically ventilated ICU patients admitted with a primary trauma diagnosis presenting to the ICU will be recruited into the study from participating study centres in Australia, New Zealand, Europe, and Saudi Arabia.
Detailed description
Trauma can cause many injuries, some of which are life-threatening and require treatment in an intensive care unit (ICU). Despite best available treatment and therapies, people who sustain a critical traumatic injury are at greater risk of death or long-term disability. From 2010 to 2015, approximately 9% of people admitted to an ICU in Australia and New Zealand for treatment of their injuries, did not survive. In Victoria, 6-months post injury, approximately 31% of people who were critically injured developed severe disabilities or died.
Following a traumatic injury, a number of complex pathways are activated by the body. These pathways can occur over hours or weeks and may lead to damage of cells, tissues or blood vessels and may destroy other healthy tissue. The treatment of traumatic injury focuses on trying to minimise further damage that can occur after the initial injury.
Erythropoietin is a glycoprotein hormone essential for erythropoiesis and was first purified in 1977. Its human recombinant analogues known as erythropoiesis stimulating agents (ESAs) are approved for human therapeutic use. However, erythropoietin is also a pleiotropic cytokine with effects beyond just erythropoiesis. Studies in animals have demonstrated the potential protective effects of erythropoietin to organs including the brain, kidney, liver and heart, and anti-inflammatory properties.
Previous research suggests the use of the ESA called epoetin alfa, increases the number of patients surviving severe trauma and reduces the risk of disability in those who survive.
The primary aim of the study is to determine the efficacy of epoetin alfa compared to placebo in reducing mortality and severe disability at six months in critically ill trauma patients.
2500 mechanically ventilated ICU patients admitted with a primary trauma diagnosis presenting to the ICU will be recruited into the study from participating study centres in Australia, New Zealand, Europe, and Saudi Arabia.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Erythropoietin (EPO) | Active comparator | Drug: Epoetin Alfa 40000 UNT/MLEpoetin alfa 40,000 IU (1mL pre-filled syringe) will be given by subcutaneous injection to eligible patients on Study Days 1 and 8 during the intensive care unit stay. |
| Placebo | Placebo comparator | Drug: Sodium Chloride 0.9%Sodium Chloride 0.9% (1mL in volume) will be given by subcutaneous injection to eligible patients allocated to the placebo arm on Study Days 1 and 8 during the intensive care unit stay. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Epoetin Alfa 40000 UNT/MLAlso: Eprex, BinocritEpoetin alfa 40,000IU 1mL pre-filled syringe given as subcutaneous injection. | Drug | Erythropoietin (EPO) |
| Sodium Chloride 0.9%Also: Placebo, SalineSodium Chloride 0.9% 1mL in volume given as subcutaneous injection. | Drug | Placebo |
Primary outcome
Combined proportion of participants who have died or have severe disability (WHODAS 2.0 > 25)
Time frame: 6-months
6 secondary outcomes
Mortality at 6-months
Time frame: 6 months
Mortality at ICU discharge
Time frame: 6-months
Mortality at Hospital discharge
Time frame: 6-months
Mortality at day 28
Time frame: 28 days
Proportion of participants with a favourable Glasgow Outcome Score Extended (GOSE) (GOSE 5-8) compared to those have have died (GOSE 1), or have severe disability (GOSE 2-4).
Time frame: 6-months
Proportion of participants with composite thrombotic vascular events (deep vein thrombosis (DVT), pulmonary embolism (PE), myocardial infarction (PI), cardiac arrest and cerebrovascular events) at 6 months.
Time frame: 6-months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jul 2025.
- Results publication: PubMed 26452709Nichol A, French C, Little L, Haddad S, Presneill J, Arabi Y, Bailey M, Cooper DJ, Duranteau J, Huet O, Mak A, McArthur C, Pettila V, Skrifvars M, Vallance S, Varma D, Wills J, Bellomo R; EPO-TBI Investigators; ANZICS Clinical Trials Group. Erythropoietin in traumatic brain injury (EPO-TBI): a double-blind randomised controlled trial. Lancet. 2015 Dec 19;386(10012):2499-506. doi: 10.1016/S0140-6736(15)00386-4. Epub 2015 Oct 6.
- Individual participant dataSharing planned: Yes. At the conclusion of the study, the study management committee will consider requests from researchers who provide a methodically sound scientific proposal as per the Data Sharing Policy set out in the ANZIC-RC Terms of Reference.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Associate Professor Craig French study chair
Western Health; ANZIC Research Centre
Professor Alistair Nichol study chair
University College Dublin
41 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Epoetin Alfa 40000 UNT/ML and Sodium Chloride 0.9% in people with Trauma and Traumatic Injury, run by Australian and New Zealand Intensive Care Research Centre at 41 sites in 9 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 16 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 41 sites in Australia, Belgium, New Zealand, Finland, Ireland and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Vicki Papanikolaou (+61 409 142 695, vicki.papanikolaou@monash.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Combined proportion of participants who have died or have severe disability (WHODAS 2.0 > 25) (time frame: 6-months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04588311, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jul 2025.