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Erythropoietin in Traumatic Brain Injury (EPO-TBI)

This study is ongoing, but not recruiting participants.
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):
Siouxzy Morrison, Australian and New Zealand Intensive Care Research Centre
ClinicalTrials.gov Identifier:
NCT00987454
First received: September 29, 2009
Last updated: November 3, 2014
Last verified: April 2014
  Purpose

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 Intervention Phase
Traumatic Brain Injury
Drug: Epoetin Alfa
Drug: Placebo, Sodium Chloride 0.9%
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomised, Placebo-controlled Trial of Erythropoietin in ICU Patients With Traumatic Brain Injury

Resource links provided by NLM:


Further study details as provided by Australian and New Zealand Intensive Care Research Centre:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 606
Study Start Date: May 2010
Estimated Study Completion Date: May 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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: Placebo, Sodium Chloride 0.9%
Sodium Chloride 0.9% 1 ml given as a subcutaneous injection weekly up to 3 doses
Other Name: Normal Saline

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.

  Eligibility

Ages Eligible for Study:   15 Years to 65 Years
Genders Eligible for Study:   Both
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00987454

  Hide Study Locations
Locations
Australia, Australian Capital Territory
Canberra Hospital
Canberra, Australian Capital Territory, Australia, 2605
Australia, New South Wales
Royal Prince Alfred Hospital
Camperdown, New South Wales, Australia, 2050
St Vincent's Hospital Sydney
Darlinghurst, New South Wales, Australia, 2010
Liverpool Hospital
Liverpool, New South Wales, Australia, 2170
John Hunter Hospital
Newcastle, New South Wales, Australia, 2305
Royal North Shore Hospital
St Leonards, New South Wales, Australia, 2065
Westmead Hospital
Westmead, New South Wales, Australia, 2145
Australia, Queensland
Gold Coast University Hospital
Southport, Queensland, Australia, 4215
The Townsville Hospital
Townsville, Queensland, Australia, 4814
Australia, South Australia
Royal Adelaide Hosptial
Adelaide, South Australia, Australia, 5000
Australia, Tasmania
Royal Hobart Hospital
Hobart, Tasmania, Australia, 7000
Australia, Victoria
The Alfred Hospital
Melbourne, Victoria, Australia, 3181
The Royal Melbourne Hospital
Melbourne, Victoria, Australia, 3050
Australia, Western Australia
Royal Perth Hospital
Perth, Western Australia, Australia
Finland
Helsinki University Central Hospital
Helsinki, Finland, 00029
Kuopio University Hospital
Kuopio, Finland, 70211
France
Hôpital Michallon
Grenoble, France, 38 043
Hôpital universitaire Caremeau
Nîmes, France, 30029
Hôpital de Bicêtre
Paris, France, 94275
Hôpital Lariboisière
Paris, France, 75 475
CHU de Rouen
Rouen, France, 76 031
Germany
Johannes Gutenberg-Universtität
Mainz, Germany, D-55131
Ireland
Beaumont Hospital
Dublin, Ireland, 9
New Zealand
Auckland City Hospital
Auckland, North Island, New Zealand, 1023
Wellington Regional Hospital
Wellington, North Island, New Zealand, 6021
Christchurch Hospital
Christchurch, South Island, New Zealand, 8011
Dunedin Hospital
Dunedin, New Zealand
Saudi Arabia
King Fahad National Guard Hospital
Riyadh, Saudi Arabia, 22490
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
  More Information

No publications provided by Australian and New Zealand Intensive Care Research Centre

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Siouxzy Morrison, Executive Officer, Australian and New Zealand Intensive Care Research Centre
ClinicalTrials.gov Identifier: NCT00987454     History of Changes
Other Study ID Numbers: ANZIC-RC/RB002
Study First Received: September 29, 2009
Last Updated: November 3, 2014
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration

Additional relevant MeSH terms:
Brain Injuries
Brain Diseases
Central Nervous System Diseases
Craniocerebral Trauma
Nervous System Diseases
Trauma, Nervous System
Wounds and Injuries
Epoetin alfa
Hematinics
Hematologic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 24, 2014