ErythroPOietin Alfa to Prevent Mortality and Reduce Severe Disability in Critically Ill TRAUMA Patients

Traumatic Brain Injury Clinical Trial

— EPO-TRAUMA  

Official title:

A Randomised, Double-blind, Placebo-controlled Trial of Erythropoietin Alfa Versus Placebo in Mechanically Ventilated Critically Ill Patients Following Traumatic Injury

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04588311
• Other study ID #: ANZIC-RC/CF001
• Secondary ID: U1111-1242-36942
• Status: Recruiting
• Phase: Phase 3
• Start date: November 9, 2020
• Est. completion date: December 31, 2025

Study information

• Verified date: October 2023
• Source: Australian and New Zealand Intensive Care Research Centre
• Contact: Vicki Papanikolaou
• Phone: +61 409 142 695
• Email: vicki.papanikolaou[@]monash.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 2500
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Blunt Injury
• Brain Injuries
• Brain Injuries, Traumatic
• Major Trauma
• Multiple Trauma
• Penetrating Injury
• Trauma
• Traumatic Brain Injury
• Traumatic Injury
• Wounds and Injuries
• Wounds, Nonpenetrating
• Wounds, Penetrating

Intervention

Drug:
• Epoetin Alfa 40000 UNT/ML
Epoetin alfa 40,000IU 1mL pre-filled syringe given as subcutaneous injection.
• Sodium Chloride 0.9%
Sodium Chloride 0.9% 1mL in volume given as subcutaneous injection.

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Cairns Hospital	Cairns	Queensland
Australia	Royal Prince Alfred Hospital	Camperdown	New South Wales
Australia	St Vincent's Hospital Sydney	Darlinghurst	New South Wales
Australia	Royal Brisbane and Women's Hospital	Herston	Queensland
Australia	St George Hospital	Kogarah	New South Wales
Australia	Liverpool Hospital	Liverpool	New South Wales
Australia	Royal Melbourne Hospital	Melbourne	Victoria
Australia	The Alfred Hospital	Melbourne	Victoria
Australia	John Hunter Hospital	New Lambton Heights	New South Wales
Australia	Royal Perth Hospital	Perth	Western Australia
Australia	Royal North Shore Hospital	Saint Leonards	New South Wales
Australia	Gold Coast University Hospital	Southport	Queensland
Australia	Royal Darwin Hospital	Tiwi	Northern Territory
Australia	Westmead Hospital	Westmead	New South Wales
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland
Finland	Helsinki University Hospital (HUS)	Helsinki
Finland	Kuopio University Hospital	Kuopio
Finland	Turku University Hospital	Turku
Germany	University Hospital Münster	Münster
Ireland	Beaumont Hospital	Beaumont
Ireland	Cork University Hospital	Cork
Ireland	St Vincent's University Hospital	Dublin
New Zealand	Middlemore Hospital	Auckland	Otahuhu
New Zealand	Christchurch Hospital	Christchurch
New Zealand	Auckland City Hospital	Grafton	Auckland
New Zealand	Waikato Hospital	Hamilton	Waikato
New Zealand	Wellington Hospital	Newtown	Wellington
Saudi Arabia	King Abdulaziz Medical City	Riyadh
Slovenia	University Medical Centre Ljubljana	Ljubljana
Slovenia	University Medical Centre Maribor	Maribor
Switzerland	University Hospital Bern	Bern
Switzerland	Lucerne Cantonal Hospital	Lucerne
Switzerland	St. Gallen Cantonal Hospital	Saint Gallen

Sponsors (9)

Lead Sponsor	Collaborator
Australian and New Zealand Intensive Care Research Centre	ANZICS Clinical Trials Group, Health Research Board, Ireland, Health Research Council, New Zealand, Irish Critical Care Clinical Trials Network, Medical Research Future Fund, Medical Research Institute of New Zealand, Monash University, University College Dublin

Countries where clinical trial is conducted

Australia,  Finland,  Germany,  Ireland,  New Zealand,  Saudi Arabia,  Slovenia,  Switzerland, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Combined proportion of participants who have died or have severe disability (WHODAS 2.0 > 25)		6-months
Secondary	Mortality at 6-months		6 months
Secondary	Mortality at ICU discharge		6-months
Secondary	Mortality at Hospital discharge		6-months
Secondary	Mortality at day 28		28 days
Secondary	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).		6-months
Secondary	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.		6-months