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Erythropoietin in Traumatic Brain Injury (EPO-TBI) (EPO-TBI)

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ClinicalTrials.gov Identifier: NCT00987454
Recruitment Status : Completed
First Posted : October 1, 2009
Last Update Posted : July 26, 2016
Sponsor:
Collaborators:
National Health and Medical Research Council, Australia
Australian and New Zealand Intensive Care Society Clinical Trials Group
Monash University
Information provided by (Responsible Party):
Australian and New Zealand Intensive Care Research Centre

Brief Summary:
This study seeks to determine if erythropoietin alpha (EPO) administered to adult critical care patients with moderate or severe traumatic brain injury improves neurological function assessed at six months after injury.

Condition or disease Intervention/treatment Phase
Traumatic Brain Injury Drug: Epoetin Alfa Drug: Sodium Chloride 0.9% Phase 3

Detailed Description:

Many people who have a traumatic brain injury (TBI) - usually from a blow to the head such as in a vehicle collision or in a fall do not survive or, if they do, suffer from long-term disability. Previous studies have shown that about 1,000 people in Australia and New Zealand suffer a moderate or severe TBI every year. With current best available treatment and therapies many of these patients sustain loss of brain function and long term disability in varying degrees.

When a patient sustains a traumatic brain injury there are two phases to the injury. First, the head-impact causes immediate damage to the brain. The secondary injury, which can evolve over hours or weeks, is a very complicated process. It involves many, linked, changes to the cells, brain chemistry, tissues or blood vessels that can destroy brain tissue. The treatment of brain injury focuses on trying to minimize the secondary injury and there is much research being done to try to find treatments that will prevent it.

Erythropoietin (EPO) has recently emerged as a drug that may help reduce secondary injury and improve brain function. It has been found to offer some protection to the brain when brain cells are deprived of their normal oxygen supply causing cells to die or be impaired.

The aim of this study is to determine if EPO reduces secondary brain injury and helps patients make a better recovery after traumatic brain injury. The investigators also plan to monitor the effect of EPO on the rate of deep vein thrombosis (DVT - blood clots in the large veins in lower extremity) in patients with moderate or severe TBI in the intensive care unit (ICU).

Study Hypothesis:

In patients with moderate (GCS 9-12) or severe (3-8) TBI, EPO therapy improves long-term neurological function assessed 6 months after injury.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 606 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomised, Placebo-controlled Trial of Erythropoietin in ICU Patients With Traumatic Brain Injury
Study Start Date : May 2010
Primary Completion Date : May 2015
Study Completion Date : May 2015

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Active Comparator: Erythropoietin
Epoetin alfa 40,000 international units will be given by subcutaneous injection to eligible patients, allocated to the treatment arm, on Study Days 1; 8 and15 during the intensive care unit stay.
Drug: Epoetin Alfa
40,000 IU given as subcutaneous injection weekly up to 3 doses
Other Name: Eprex
Placebo Comparator: Placebo
Sodium Chloride 0.9% in m/L will be given by subcutaneous injection to eligible patients, allocated to the placebo arm, on Study Days 1; 8 and15 during the intensive care unit stay.
Drug: Sodium Chloride 0.9%
1 m/L given as subcutaneous injection weekly up to 3 doses
Other Name: Normal Saline



Primary Outcome Measures :
  1. Combined proportion of unfavourable neurological outcomes at 6 months: severe disability (defined as GOSE scores 2-4) or death (GOSE score 1). [ Time Frame: 6 months ]

Secondary Outcome Measures :
  1. Probability of an equal or greater Glasgow Coma Scale Extended (GOSE) level at 6 months compared to the probability of a lesser GOSE level, using a proportional odds model [ Time Frame: 6 months ]
  2. Proportion of surviving patients with unfavourable neurological outcome (GOSE 2-4) at 6 months [ Time Frame: 6 months ]
  3. Quality of life assessment (SF-12 and EQ-5D) at 6 months [ Time Frame: 6 months ]
  4. Mortality at 6 months [ Time Frame: 6 months ]
  5. Rate of proximal deep venous thrombosis detected during screening by compression Doppler ultrasound [ Time Frame: 21 days ]
  6. Proportion of patients with composite thrombotic vascular events (DVT, pulmonary embolus, myocardial infarction, cardiac arrest and cerebrovascular events) at 6 months [ Time Frame: 6 months ]
  7. Cost effectiveness analysis at 6 months (based on EQ-5D) [ Time Frame: 6 months ]


Information from the National Library of Medicine

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Ages Eligible for Study:   15 Years to 65 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Are ≥ 15 to ≤ 65 years of age
  • Are < 24 hours since primary traumatic injury
  • Are expected to stay ≥ 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 written informed consent from legal surrogate

Exclusion Criteria:

  • GCS = 3 and fixed dilated pupils
  • History of DVT, PE or other thromboembolic event
  • 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 post partum
  • Uncontrolled hypertension (systolic blood pressure of >200 mm Hg or diastolic blood pressure of >110 mm Hg)
  • Acute myocardial infarct
  • Expected to die imminently (< 24 hours)
  • Inability to perform lower limb ultrasounds
  • Known sensitivity to mammalian cell derived products
  • Hypersensitivity to the active substance or to any of the additives
  • Pure red cell aplasia (PRCA)
  • 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
  • Spinal cord injury
  • Treatment with any investigational drug within 30 days before enrolment
  • 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): NCT00987454


  Show 28 Study Locations
Sponsors and Collaborators
Australian and New Zealand Intensive Care Research Centre
National Health and Medical Research Council, Australia
Australian and New Zealand Intensive Care Society Clinical Trials Group
Monash University
Investigators
Study Chair: Alistair D Nichol, MD Monash University

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Australian and New Zealand Intensive Care Research Centre
ClinicalTrials.gov Identifier: NCT00987454     History of Changes
Other Study ID Numbers: ANZIC-RC/RB002
First Posted: October 1, 2009    Key Record Dates
Last Update Posted: July 26, 2016
Last Verified: July 2016

Additional relevant MeSH terms:
Wounds and Injuries
Brain Injuries
Brain Injuries, Traumatic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System
Epoetin Alfa
Hematinics