Erythropoietin in Traumatic Brain Injury (EPO-TBI)

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 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: August 6, 2014
Last verified: April 2014
  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 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: April 2015 (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
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

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

  Hide Study Locations
Locations
Australia, Australian Capital Territory
Canberra Hospital Recruiting
Canberra, Australian Capital Territory, Australia, 2605
Contact: Frank Van Haren, MD    +61 2 6244 2222    frank.vanharen@act.gov.au   
Principal Investigator: Frank Van Haren, 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@med.usyd.edu.au   
Principal Investigator: David Gattas, MD         
St Vincent's Hospital Sydney Active, not recruiting
Darlinghurst, New South Wales, Australia, 2010
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 Active, not recruiting
Newcastle, New South Wales, Australia, 2305
Nepean Hospital 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 9463 2633    sfinfer@george.org.au   
Principal Investigator: Simon Finfer, MD         
Westmead Hospital Recruiting
Westmead, New South Wales, Australia, 2145
Contact: Vineet Nayyar, MD    +61 2 9845 5555    vineet.nayyar@health.nsw.gov.au   
Principal Investigator: Vineet Nayyar, MD         
Australia, Queensland
Gold Coast University Hospital Active, not recruiting
Southport, Queensland, Australia, 4215
The Townsville Hospital Active, not recruiting
Townsville, Queensland, Australia, 4814
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 Active, not recruiting
Hobart, Tasmania, Australia, 7000
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         
Finland
Helsinki University Central Hospital Recruiting
Helsinki, Finland, 00029
Contact: Ville Pettila, MD       Ville.Pettila@hus.fi   
Contact: Markus Skrivfars, MD    +358 9 47187383 ext 383    Markus.Skrifvars@hus.fi   
Principal Investigator: Ville Pettila, MD         
Principal Investigator: Markus Skrifvars, MD         
Kuopio University Hospital Recruiting
Kuopio, Finland, 70211
Contact: Stepani Bendel, MD       stepani.bendel@kuh.fi   
Principal Investigator: Stepani Bendel, MD         
France
Hôpital Michallon Recruiting
Grenoble, France, 38 043
Contact: Jean François Payen, MD       Jean-Francois.Payen@ujf-grenoble.fr   
Principal Investigator: Jean François Payen, MD         
Hôpital universitaire Caremeau Recruiting
Nîmes, France, 30029
Contact: Jean Yves Lefrant, MD       jean-yves.lefrant@wanadoo.fr   
Principal Investigator: Jean Yves Lefrant, MD         
Hôpital de Bicêtre Recruiting
Paris, France, 94275
Contact: Jacques Duranteau, MD       jacques.duranteau@bct.aphp.fr   
Contact: Anatole Harrois, MD       anatole.harrois@bct.aphp.fr   
Principal Investigator: Jacques Duranteau, MD         
Hôpital Lariboisière Recruiting
Paris, France, 75 475
Contact: Didier Payen, MD       didier.payen@lrb.aphp.fr   
Principal Investigator: Didier Payen, MD         
CHU de Rouen Recruiting
Rouen, France, 76 031
Contact: Benoit Veber, MD         
Principal Investigator: Benoit Veber, MD         
Hôpital Rangueil Recruiting
Toulouse, France, 31059
Contact: Thomas Geeraerts, MD       thgeeraerts@hotmail.com   
Principal Investigator: Thomas Geeraerts, MD         
Hôpital Purpan Not yet recruiting
Toulouse, France, 31059
Contact: Julie Motuel, MD       motuel.j@chu-toulouse.fr   
Principal Investigator: Julie Motuel, MD         
Germany
Johannes Gutenberg-Universtität Recruiting
Mainz, Germany, D-55131
Contact: Thomas Kerz, MD       kerz@uni-mainz.de   
Principal Investigator: Thomas Kerz, MD         
Ireland
Beaumont Hospital Recruiting
Dublin, Ireland, 9
Contact: Criona Walshe, MD    00 353 86 6061089    criona.walshe@beaumont.ie   
Principal Investigator: Criona Walshe, 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         
Dunedin Hospital Recruiting
Dunedin, New Zealand
Contact: Matthew Bailey, MD       Mat.bailey@southerndhb.govt.nz   
Principal Investigator: Matthew Bailey, 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
Transport Accident Commission
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: August 6, 2014
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration

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

ClinicalTrials.gov processed this record on August 21, 2014