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ErythroPOietin Alfa to Prevent Mortality and Reduce Severe Disability in Critically Ill TRAUMA Patients (EPO-TRAUMA)

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ClinicalTrials.gov Identifier: NCT04588311
Recruitment Status : Recruiting
First Posted : October 19, 2020
Last Update Posted : November 12, 2020
Sponsor:
Collaborators:
University College Dublin
Medical Research Institute of New Zealand
Medical Research Future Fund (MRFF)
Health Research Board, Ireland
Health Research Council, New Zealand
Irish Critical Care Clinical Trials Network
ANZICS Clinical Trials Group
Monash University
Information provided by (Responsible Party):
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.


Condition or disease Intervention/treatment Phase
Trauma Traumatic Injury Traumatic Brain Injury Wounds and Injuries Penetrating Injury Blunt Injury Major Trauma Multiple Trauma Drug: Epoetin Alfa 40000 UNT/ML Drug: Sodium Chloride 0.9% Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 2500 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomised, Double-blind, Placebo-controlled Trial of Erythropoietin Alfa Versus Placebo in Mechanically Ventilated Critically Ill Patients Following Traumatic Injury
Actual Study Start Date : November 9, 2020
Estimated Primary Completion Date : March 31, 2025
Estimated Study Completion Date : March 31, 2025

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Erythropoietin (EPO)
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.
Drug: Epoetin Alfa 40000 UNT/ML
Epoetin alfa 40,000IU 1mL pre-filled syringe given as subcutaneous injection.
Other Names:
  • Eprex
  • Binocrit

Placebo Comparator: Placebo
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.
Drug: Sodium Chloride 0.9%
Sodium Chloride 0.9% 1mL in volume given as subcutaneous injection.
Other Names:
  • Placebo
  • Saline




Primary Outcome Measures :
  1. Combined proportion of participants who have died or have severe disability (WHODAS 2.0 > 25) [ Time Frame: 6-months ]

Secondary Outcome Measures :
  1. Mortality at 6-months [ Time Frame: 6 months ]
  2. Mortality at ICU discharge [ Time Frame: 6-months ]
  3. Mortality at Hospital discharge [ Time Frame: 6-months ]
  4. Mortality at day 28 [ Time Frame: 28 days ]
  5. 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 ]
  6. 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 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04588311


Contacts
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Contact: Vicki Papanikolaou +61 3 9905 6645 vicki.papanikolaou@monash.edu
Contact: Liadain Reid +353 (0) 716 5810 liadain.reid@ucd.ie

Locations
Show Show 17 study locations
Sponsors and Collaborators
Australian and New Zealand Intensive Care Research Centre
University College Dublin
Medical Research Institute of New Zealand
Medical Research Future Fund (MRFF)
Health Research Board, Ireland
Health Research Council, New Zealand
Irish Critical Care Clinical Trials Network
ANZICS Clinical Trials Group
Monash University
Investigators
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Study Chair: A/Professor Craig French Western Health; ANZIC Research Centre
Study Chair: Professor Alistair Nichol University College Dublin; ANZIC Research Centre
Publications of Results:
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Responsible Party: Australian and New Zealand Intensive Care Research Centre
ClinicalTrials.gov Identifier: NCT04588311    
Other Study ID Numbers: ANZIC-RC/CF001
U1111-1242-3694 ( Registry Identifier: Australian New Zealand Clinical Trials Registry (ANZCTR) )
2020-003388-24 ( EudraCT Number )
First Posted: October 19, 2020    Key Record Dates
Last Update Posted: November 12, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: 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.
Time Frame: As per the ANZIC Research Centre Data Sharing Policy
Access Criteria: As per the ANZIC Research Centre Data Sharing Policy
URL: https://www.monash.edu/__data/assets/pdf_file/0010/2153899/2020-03-19-ANZIC-RC-Terms-of-Reference.pdf

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Australian and New Zealand Intensive Care Research Centre:
Intensive Care Unit
Trauma
Major trauma
Traumatic injury
EPO
Erythropoietin
Epoetin alfa
Additional relevant MeSH terms:
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Brain Injuries
Brain Injuries, Traumatic
Wounds and Injuries
Multiple Trauma
Wounds, Nonpenetrating
Wounds, Penetrating
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System
Epoetin Alfa
Hematinics