Erythropoietin in Traumatic Brain Injury (EPO-TBI)

NCT ID: NCT00987454

Last Updated: 2016-07-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

606 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-05-31

Study Completion Date

2015-05-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Traumatic Brain Injury

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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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.

Group Type ACTIVE_COMPARATOR

Epoetin Alfa

Intervention Type DRUG

40,000 IU given as subcutaneous injection weekly up to 3 doses

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.

Group Type PLACEBO_COMPARATOR

Sodium Chloride 0.9%

Intervention Type DRUG

1 m/L given as subcutaneous injection weekly up to 3 doses

Interventions

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Epoetin Alfa

40,000 IU given as subcutaneous injection weekly up to 3 doses

Intervention Type DRUG

Sodium Chloride 0.9%

1 m/L given as subcutaneous injection weekly up to 3 doses

Intervention Type DRUG

Other Intervention Names

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Eprex Normal Saline

Eligibility Criteria

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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
Minimum Eligible Age

15 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Health and Medical Research Council, Australia

OTHER

Sponsor Role collaborator

Australian and New Zealand Intensive Care Society Clinical Trials Group

NETWORK

Sponsor Role collaborator

Monash University

OTHER

Sponsor Role collaborator

Australian and New Zealand Intensive Care Research Centre

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Alistair D Nichol, MD

Role: STUDY_CHAIR

Monash University

Locations

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Canberra Hospital

Canberra, Australian Capital Territory, Australia

Site Status

Royal Prince Alfred Hospital

Camperdown, New South Wales, Australia

Site Status

St Vincent's Hospital Sydney

Darlinghurst, New South Wales, Australia

Site Status

Liverpool Hospital

Liverpool, New South Wales, Australia

Site Status

John Hunter Hospital

Newcastle, New South Wales, Australia

Site Status

Royal North Shore Hospital

St Leonards, New South Wales, Australia

Site Status

Westmead Hospital

Westmead, New South Wales, Australia

Site Status

Gold Coast University Hospital

Southport, Queensland, Australia

Site Status

The Townsville Hospital

Townsville, Queensland, Australia

Site Status

Royal Adelaide Hosptial

Adelaide, South Australia, Australia

Site Status

Royal Hobart Hospital

Hobart, Tasmania, Australia

Site Status

The Royal Melbourne Hospital

Melbourne, Victoria, Australia

Site Status

The Alfred Hospital

Melbourne, Victoria, Australia

Site Status

Royal Perth Hospital

Perth, Western Australia, Australia

Site Status

Helsinki University Central Hospital

Helsinki, , Finland

Site Status

Kuopio University Hospital

Kuopio, , Finland

Site Status

Hôpital Michallon

Grenoble, , France

Site Status

Hôpital universitaire Caremeau

Nîmes, , France

Site Status

Hôpital Lariboisière

Paris, , France

Site Status

Hôpital de Bicêtre

Paris, , France

Site Status

CHU de Rouen

Rouen, , France

Site Status

Johannes Gutenberg-Universtität

Mainz, , Germany

Site Status

Beaumont Hospital

Dublin, , Ireland

Site Status

Auckland City Hospital

Auckland, North Island, New Zealand

Site Status

Wellington Regional Hospital

Wellington, North Island, New Zealand

Site Status

Christchurch Hospital

Christchurch, South Island, New Zealand

Site Status

Dunedin Hospital

Dunedin, , New Zealand

Site Status

King Fahad National Guard Hospital

Riyadh, , Saudi Arabia

Site Status

Countries

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Australia Finland France Germany Ireland New Zealand Saudi Arabia

References

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Nishiwaki H, Abe Y, Suzuki T, Hasegawa T, Levack WM, Noma H, Ota E. Erythropoiesis-stimulating agents for preventing acute kidney injury. Cochrane Database Syst Rev. 2024 Sep 20;9(9):CD014820. doi: 10.1002/14651858.CD014820.pub2.

Reference Type DERIVED
PMID: 39301879 (View on PubMed)

Skrifvars MB, Bailey M, Moore E, Martensson J, French C, Presneill J, Nichol A, Little L, Duranteau J, Huet O, Haddad S, Arabi YM, McArthur C, Cooper DJ, Bendel S, Bellomo R; Erythropoietin in Traumatic Brain Injury (EPO-TBI) Investigators and the Australian and New Zealand Intensive Care Society (ANZICS) Clinical Trials Group. A Post Hoc Analysis of Osmotherapy Use in the Erythropoietin in Traumatic Brain Injury Study-Associations With Acute Kidney Injury and Mortality. Crit Care Med. 2021 Apr 1;49(4):e394-e403. doi: 10.1097/CCM.0000000000004853.

Reference Type DERIVED
PMID: 33566466 (View on PubMed)

Skrifvars MB, Moore E, Martensson J, Bailey M, French C, Presneill J, Nichol A, Little L, Duranteau J, Huet O, Haddad S, Arabi Y, McArthur C, Cooper DJ, Bellomo R; EPO-TBI Investigators and the ANZICS Clinical Trials Group. Erythropoietin in traumatic brain injury associated acute kidney injury: A randomized controlled trial. Acta Anaesthesiol Scand. 2019 Feb;63(2):200-207. doi: 10.1111/aas.13244. Epub 2018 Aug 21.

Reference Type DERIVED
PMID: 30132785 (View on PubMed)

Nichol A, French C, Little L, Haddad S, Presneill J, Arabi Y, Bailey M, Cooper DJ, Duranteau J, Huet O, Mak A, McArthur C, Pettila V, Skrifvars M, Vallance S, Varma D, Wills J, Bellomo R; EPO-TBI Investigators; ANZICS Clinical Trials Group. Erythropoietin in traumatic brain injury (EPO-TBI): a double-blind randomised controlled trial. Lancet. 2015 Dec 19;386(10012):2499-506. doi: 10.1016/S0140-6736(15)00386-4. Epub 2015 Oct 6.

Reference Type DERIVED
PMID: 26452709 (View on PubMed)

Nichol A, French C, Little L, Presneill J, Cooper DJ, Haddad S, Duranteau J, Huet O, Skrifvars M, Arabi Y, Bellomo R; EPO-TBI Investigators and the Australian and New Zealand Intensive Care Society Clinical Trials Group. Erythropoietin in traumatic brain injury: study protocol for a randomised controlled trial. Trials. 2015 Feb 8;16:39. doi: 10.1186/s13063-014-0528-6.

Reference Type DERIVED
PMID: 25884605 (View on PubMed)

Presneill J, Little L, Nichol A, French C, Cooper DJ, Haddad S, Duranteau J, Huet O, Skrifvars M, Arabi Y, Bellomo R; EPO-TBI Investigators; ANZICS Clinical Trials Group. Statistical analysis plan for the Erythropoietin in Traumatic Brain Injury trial: a randomised controlled trial of erythropoietin versus placebo in moderate and severe traumatic brain injury. Trials. 2014 Dec 20;15:501. doi: 10.1186/1745-6215-15-501.

Reference Type DERIVED
PMID: 25528574 (View on PubMed)

Moore EM, Bellomo R, Nichol AD. Erythropoietin as a novel brain and kidney protective agent. Anaesth Intensive Care. 2011 May;39(3):356-72. doi: 10.1177/0310057X1103900306.

Reference Type DERIVED
PMID: 21675055 (View on PubMed)

Other Identifiers

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ANZIC-RC/RB002

Identifier Type: -

Identifier Source: org_study_id

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