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

Phase 3

Recruiting

• Conditions: Traumatic Injury; Traumatic Brain Injury; Blunt Injury; Wounds and Injuries; Major Trauma; Penetrating Injury; Trauma; Multiple Trauma
• Interventions: Drug: Epoetin Alfa 40000 UNT/ML; Drug: Sodium Chloride 0.9%

• Registration Number: NCT04588311
• Lead Sponsor: Australian and New Zealand Intensive Care Research Centre

Brief 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.

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 Timeline

• Study First Submitted: 2020-10-01
• Study First Submitted QC: 2020-10-08
• Study First Posted: 2020-10-19
• Study Start: 2020-11-09
• Status Verified: 2023-10
• Last Update Submitted: 2023-10-01
• Last Update Posted: 2023-10-03
• Primary Completion: 2025-12-31
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 2500

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Erythropoietin (EPO)	Epoetin Alfa 40000 UNT/ML	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.
Placebo	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.

Primary Outcome Measures

Name	Time	Method
Combined proportion of participants who have died or have severe disability (WHODAS 2.0 > 25)	6-months

Secondary Outcome Measures

Name	Time	Method
Mortality at ICU discharge	6-months
Mortality at day 28	28 days
Mortality at 6-months	6 months
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
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
Mortality at Hospital discharge	6-months

Trial Locations

Locations (34)

King Abdulaziz Medical City; 🇸🇦 Riyadh, Saudi Arabia

Cork University Hospital; 🇮🇪 Cork, Ireland

St. Gallen Cantonal Hospital; 🇨🇭 Saint Gallen, Switzerland

Royal Melbourne Hospital; 🇦🇺 Melbourne, Victoria, Australia

Helsinki University Hospital (HUS); 🇫🇮 Helsinki, Finland

Kuopio University Hospital; 🇫🇮 Kuopio, Finland

Beaumont Hospital; 🇮🇪 Beaumont, Ireland

University Medical Centre Ljubljana; 🇸🇮 Ljubljana, Slovenia

University Medical Centre Maribor; 🇸🇮 Maribor, Slovenia

University Hospital Bern; 🇨🇭 Bern, Switzerland

Royal Prince Alfred Hospital; 🇦🇺 Camperdown, New South Wales, Australia

St Vincent's Hospital Sydney; 🇦🇺 Darlinghurst, New South Wales, Australia

Liverpool Hospital; 🇦🇺 Liverpool, New South Wales, Australia

St George Hospital; 🇦🇺 Kogarah, New South Wales, Australia

Royal North Shore Hospital; 🇦🇺 Saint Leonards, New South Wales, Australia

John Hunter Hospital; 🇦🇺 New Lambton Heights, New South Wales, Australia

Westmead Hospital; 🇦🇺 Westmead, New South Wales, Australia

Cairns Hospital; 🇦🇺 Cairns, Queensland, Australia

Gold Coast University Hospital; 🇦🇺 Southport, Queensland, Australia

Princess Alexandra Hospital; 🇦🇺 Woolloongabba, Queensland, Australia

Royal Adelaide Hospital; 🇦🇺 Adelaide, South Australia, Australia

The Alfred Hospital; 🇦🇺 Melbourne, Victoria, Australia

University Hospital Münster; 🇩🇪 Münster, Germany

Royal Perth Hospital; 🇦🇺 Perth, Western Australia, Australia

Turku University Hospital; 🇫🇮 Turku, Finland

Auckland City Hospital; 🇳🇿 Grafton, Auckland, New Zealand

Middlemore Hospital; 🇳🇿 Auckland, Otahuhu, New Zealand

Waikato Hospital; 🇳🇿 Hamilton, Waikato, New Zealand

St Vincent's University Hospital; 🇮🇪 Dublin, Ireland

Wellington Hospital; 🇳🇿 Newtown, Wellington, New Zealand

Christchurch Hospital; 🇳🇿 Christchurch, New Zealand

Lucerne Cantonal Hospital; 🇨🇭 Lucerne, Switzerland

Royal Brisbane and Women's Hospital; 🇦🇺 Herston, Queensland, Australia

Royal Darwin Hospital; 🇦🇺 Tiwi, Northern Territory, Australia