Erythropoietin in Traumatic Brain Injury (EPO-TBI)

This study is currently recruiting participants.
Verified February 2013 by Australian and New Zealand Intensive Care Research Centre
Sponsor:
Collaborators:
National Health and Medical Research Council, Australia
Transport Accident Commission
Australian and New Zealand Intensive Care Society Clinical Trials Group
Monash University
Information provided by (Responsible Party):
Siouxzy Morrison, Australian and New Zealand Intensive Care Research Centre
ClinicalTrials.gov Identifier:
NCT00987454
First received: September 29, 2009
Last updated: May 27, 2013
Last verified: February 2013

September 29, 2009
May 27, 2013
May 2010
May 2014   (final data collection date for primary outcome measure)
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 ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00987454 on ClinicalTrials.gov Archive Site
  • 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 ] [ Designated as safety issue: No ]
  • Proportion of surviving patients with unfavourable neurological outcome (GOSE 2-4) at 6 months [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Quality of life assessment (SF-12 and EQ-5D) at 6 months [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Mortality at 6 months [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Rate of proximal deep venous thrombosis detected during screening by compression Doppler ultrasound [ Time Frame: up to ICU discharge ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • Cost effectiveness analysis at 6 months (based on EQ-5D) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Probability of an equal or greater GOSE level at 6 months compared to the probability of a lesser GOSE level, using a proportional odds model [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Proportion of surviving patients with unfavourable neurological outcome (GOSE 2-4) at 6 months [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Quality of life assessment (SF-12 and EQ-5D) at 6 months [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Mortality at 6 months [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Rate of proximal deep venous thrombosis detected during screening by compression Doppler ultrasound [ Time Frame: up to ICU discharge ] [ Designated as safety issue: Yes ]
  • Proportion of patients with composite thrombotic vascular events (DVT, PE, myocardial infarction, cardiac arrest and cerebrovascular events) at 6 months [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Duration and incidence of organ failure [ Time Frame: up to ICU discharge ] [ Designated as safety issue: No ]
  • Cost effectiveness analysis at 6 months (based on EQ-5D) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Erythropoietin in Traumatic Brain Injury (EPO-TBI)
A Randomised, Placebo-controlled Trial of Erythropoietin in ICU Patients With Traumatic Brain Injury

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.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Traumatic Brain Injury
  • Drug: Epoetin Alfa
    40,000 IU given as subcutaneous injection weekly up to 3 doses
  • Drug: Placebo, Sodium Chloride
    1 ml given as a subcutaneous injection weekly up to 3 doses
  • Active Comparator: Erythropoietin
    Intervention: Drug: Epoetin Alfa
  • Placebo Comparator: Placebo
    Intervention: Drug: Placebo, Sodium Chloride
Moore EM, Bellomo R, Nichol AD. Erythropoietin as a novel brain and kidney protective agent. Anaesth Intensive Care. 2011 May;39(3):356-72. Review.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
606
August 2014
May 2014   (final data collection date for primary outcome measure)

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
Both
15 Years to 65 Years
No
Contact: Rinaldo Bellomo, MD +61 3 9496 5992 Rinaldo.BELLOMO@austin.org.au
Contact: Lorraine M Little, RN BHSc(Nursing) MBioethics +61 3 9903 0513 lorraine.little@monash.edu
Australia,   Finland,   France,   Germany,   Ireland,   New Zealand,   Saudi Arabia,   Singapore
 
NCT00987454
ANZIC-RC/RB002
Yes
Siouxzy Morrison, Australian and New Zealand Intensive Care Research Centre
Australian and New Zealand Intensive Care Research Centre
  • National Health and Medical Research Council, Australia
  • Transport Accident Commission
  • Australian and New Zealand Intensive Care Society Clinical Trials Group
  • Monash University
Study Chair: Alistair D Nichol, MD Monash University
Australian and New Zealand Intensive Care Research Centre
February 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP