Erythropoietin in Traumatic Brain Injury (EPO-TBI) - Full Text View

Sponsor:	Australian and New Zealand Intensive Care Research Centre
Collaborators:	National Health and Medical Research Council, Australia Victorian Neurotrauma Initiative 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

Purpose

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.

Condition	Intervention	Phase
Traumatic Brain Injury	Drug: Epoetin Alfa Drug: Placebo, Sodium Chloride	Phase III

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:

MedlinePlus related topics: Traumatic Brain Injury

Drug Information available for: Erythropoietin Chlorides Epoetin alfa Sodium chloride

U.S. FDA Resources

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 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 ]
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:	August 2014
Estimated Primary Completion Date:	May 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Erythropoietin	Drug: Epoetin Alfa 40,000 IU given as subcutaneous injection weekly up to 3 doses
Placebo Comparator: Placebo	Drug: Placebo, Sodium Chloride 1 ml given as a subcutaneous injection weekly up to 3 doses

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

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

Contacts

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

Locations

Australia, Australian Capital Territory
Canberra Hospital	Recruiting
Canberra, Australian Capital Territory, Australia, 2605
Contact: Imogen Mitchell, MD +61 2 6244 2222 imogen.mitchell@act.gov.au
Principal Investigator: Imogen Mitchell, MD
Australia, New South Wales
Royal Prince Alfred Hospital	Recruiting
Camperdown, New South Wales, Australia, 2050
Contact: David Gattas, MD +61 2 9515 6111 dgattas@gmail.com
Principal Investigator: David Gattas, MD
St Vincent's Hospital Sydney	Recruiting
Darlinghurst, New South Wales, Australia, 2010
Contact: Priya Nair, MD +61 2 8382 1111 pnair@stvincents.com.au
Principal Investigator: Priya Nair, MD
Liverpool Hospital	Recruiting
Liverpool, New South Wales, Australia, 2170
Contact: Victor Tam, MD +61 2 9828 3000 victor.tam@sswahs.nsw.gov.au
Principal Investigator: Victor Tam, MD
John Hunter Hospital	Not yet recruiting
Newcastle, New South Wales, Australia, 2305
Contact: Peter Harrigan, MD +61 2 49213000 peter.harrigan@hnehealth.nsw.gov.au
Principal Investigator: Peter Harrigan, MD
Nepean Hospital	Not yet recruiting
Penrith, New South Wales, Australia, 2750
Contact: Louise Cole, MD +61 2 4734 2000 colel@med.usyd.edu.au
Principal Investigator: Louise Cole, MD
Royal North Shore Hospital	Recruiting
St Leonards, New South Wales, Australia, 2065
Contact: Simon Finfer, MD +61 2 9926 8656 sfinfer@george.org.au
Principal Investigator: Simon Finfer, MD
Westmead Hospital	Not yet recruiting
Westmead, New South Wales, Australia, 2145
Contact: Vineet Nayyar, MD +61 2 9845 5555 Vineet_Nayyar@wsahs.nsw.gov.au
Principal Investigator: Vineet Nayyar, MD
Australia, Queensland
Gold Coast Hospital	Recruiting
Southport, Queensland, Australia, 4215
Contact: Brent Richards, MD +61 7 5519 8211 BRENT_RICHARDS@HEALTH.QLD.GOV.AU
Principal Investigator: Brent Richards, MD
The Townsville Hospital	Recruiting
Townsville, Queensland, Australia, 4814
Contact: Geoffrey Gordon, MD +61 7 4796 1111 geoffrey_gordon@health.qld.gov.au
Principal Investigator: Geoffrey Gordon, MD
Australia, South Australia
Royal Adelaide Hosptial	Recruiting
Adelaide, South Australia, Australia, 5000
Contact: Richard Strickland, MD +61 8 8222 4000 rich.stricko@gmail.com
Principal Investigator: Richard Strickland, MD
Australia, Tasmania
Royal Hobart Hospital	Recruiting
Hobart, Tasmania, Australia, 7000
Contact: David Cooper, MD +61 3 6222 8308 david.cooper@dhhs.tas.gov.au
Principal Investigator: David Cooper, MD
Australia, Victoria
The Alfred Hospital	Recruiting
Melbourne, Victoria, Australia, 3181
Contact: David J Cooper, MD +61 3 9076 2000 j.cooper@alfred.org.au
Principal Investigator: David J Cooper, MD
The Royal Melbourne Hospital	Recruiting
Melbourne, Victoria, Australia, 3050
Contact: Nerina Harley, MD +61 3 9342 7000 ext 27441 nerina.harley@mh.org.au
Principal Investigator: Nerina Harley, MD
Australia, Western Australia
Royal Perth Hospital	Recruiting
Perth, Western Australia, Australia
Contact: Geoffrey Dobb, MD +61 8 9224 2244 geoffrey.dobb@health.wa.gov.au
Principal Investigator: Geoffrey Dobb, MD
New Zealand
Auckland City Hospital	Recruiting
Auckland, North Island, New Zealand, 1023
Contact: Colin McArthur, MD + 64 9 379 7440 colinm@adhb.govt.nz
Principal Investigator: Colin McArthur, MD
Wellington Regional Hospital	Recruiting
Wellington, North Island, New Zealand, 6021
Contact: Richard Dinsdale, MD + 64 4 385 5999 dick.dinsdale@ccdhb.org.nz
Principal Investigator: Richard Dinsdale, MD
Christchurch Hospital	Recruiting
Christchurch, South Island, New Zealand, 8011
Contact: Seton Henderson, MD + 64 3 3640640 seton.henderson@cdhb.govt.nz
Principal Investigator: Seton Henderson, MD
Saudi Arabia
King Fahad National Guard Hospital	Recruiting
Riyadh, Saudi Arabia, 22490
Contact: Samir Haddad, MD 996612520088 ext 18923 haddadS@NGHA.MED.SA
Principal Investigator: Samir Haddad, MD

Sponsors and Collaborators

Australian and New Zealand Intensive Care Research Centre

National Health and Medical Research Council, Australia

Victorian Neurotrauma Initiative

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):

Moore EM, Bellomo R, Nichol AD. Erythropoietin as a novel brain and kidney protective agent. Anaesth Intensive Care. 2011 May;39(3):356-72.

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:	September 6, 2011
Health Authority:	Australia: Department of Health and Ageing Therapeutic Goods Administration

Additional relevant MeSH terms:

Brain Injuries
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System

Wounds and Injuries
Epoetin Alfa
Hematinics
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on February 09, 2012