ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12609000827235

Ethics application status

Approved

Date submitted

22/09/2009

Date registered

22/09/2009

Date last updated

28/08/2015

Type of registration

Prospectively registered

Titles & IDs

Public title

Erythropoietin in Traumatic Brain Injury (EPO-TBI)

Scientific title

A randomised, placebo-controlled trial evaluating the effect of erythropoietin on neurological function in intensive care unit (ICU) patients with traumatic brain injury

Secondary ID [1]

None

Universal Trial Number (UTN)

None

Trial acronym

EPO-TBI = erythropoietin in traumatic brain injury

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Moderate traumatic brain injury

Severe traumatic brain injury

Condition category

Condition code

Injuries and Accidents

Other injuries and accidents

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Epoetin alfa (rch) 40,000 units, volume of 1mililitre, given as a subcutaneous injection weekly for up to 3 doses.

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

Sodium Chloride 0.9%, 1 mililitre, will be given as a subcutaneous injection weekly for up to 3 doses.

Control group

Placebo

Outcomes

Primary outcome [1]

Combined proportion of unfavourable neurological outcomes at 6 months: severe disability (defined as Glasgow Outcome Scale - Extended [GOSE] scores 2-4) or death (GOSE score 1).

Timepoint [1]

6 months after traumatic brain injury

Secondary outcome [1]

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

Timepoint [1]

6 months after traumatic brain injury

Secondary outcome [2]

Proportion of surviving patients with unfavourable neurological outcome (GOSE 2-4) at 6 months

Timepoint [2]

6 months after traumatic brain injury

Secondary outcome [3]

Quality of life assessment (SF-12 and EQ-5D) at 6 months

Timepoint [3]

6 months after traumatic brain injury

Secondary outcome [4]

All-cause mortality assessed via clinical database.

Timepoint [4]

6 months after traumatic brain injury

Secondary outcome [5]

Rate of proximal deep venous thrombosis (DVT) detected during screening by compression Doppler ultrasound

Timepoint [5]

Up to ICU discharge

Secondary outcome [6]

Proportion of patients with composite thrombotic vascular events (DVT, Pulmonary Embolism (PE), myocardial infarction, cardiac arrest and cerebrovascular events) at 6 months

Timepoint [6]

6 months after traumatic brain injury

Secondary outcome [7]

Cost-effectiveness analysis for patients enrolled in the study based on the questionnaire EQ-5D.

Timepoint [7]

6 months after traumatic brain injury

Eligibility

Key inclusion criteria

Admitted to ICU with non-penetrating traumatic brain injury
15 to 65 years of age
Less than 24 hours since primary traumatic injury
Expected to stay greater than or equal to 48 hours
Have a haemoglobin not exceeding the upper limit of the applicable normal (ULN) reference range in clinical use at the treating institution
Written informed consent from legal surrogate

Minimum age

15 Years

Maximum age

65 Years

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

Glasgow Coma Score (GCS) is 3 and pupils are fixed and dilated; 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 greater than 200 mm Hg or diastolic blood pressure of greater than 110 mm Hg); Acute myocardial infarct; Expected to die imminently (within 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.

Study design

Purpose of the study

Treatment

Allocation to intervention

Randomised controlled trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Central randomisation via computer

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Computerised sequence generation using block randomisation. Randomisation will be stratified by site and by Glasgow Coma Score; severe TBI (GCS 3-8) or moderate TBI (GCS 9-12)

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

Intervention assignment

Parallel

Other design features

Phase

Phase 3

Type of endpoint/s

Safety/efficacy

Statistical methods / analysis

Recruitment

Recruitment status

Completed

Date of first participant enrolment

Anticipated

1/02/2010

Actual

18/05/2010

Date of last participant enrolment

Anticipated

Actual

1/11/2014

Date of last data collection

Anticipated

Actual

Sample size

Target

606

Accrual to date

Final

606

Recruitment in Australia

Recruitment state(s)

Recruitment postcode(s) [1]

2605

Recruitment postcode(s) [2]

2750

Recruitment postcode(s) [3]

2065

Recruitment postcode(s) [4]

2010

Recruitment postcode(s) [5]

2050

Recruitment postcode(s) [6]

2145

Recruitment postcode(s) [7]

2170

Recruitment postcode(s) [8]

4215

Recruitment postcode(s) [9]

4814

Recruitment postcode(s) [10]

3050

Recruitment postcode(s) [11]

3181

Recruitment postcode(s) [12]

5000

Recruitment postcode(s) [13]

7000

Recruitment postcode(s) [14]

6000 - Perth

Recruitment outside Australia

Country [1]

New Zealand

State/province [1]

Auckland

Country [2]

New Zealand

State/province [2]

Wellington

Country [3]

New Zealand

State/province [3]

Christchurch

Country [4]

Saudi Arabia

State/province [4]

Riyadh

Country [5]

New Zealand

State/province [5]

Dunedin

Funding & Sponsors

Funding source category [1]

Government body

Name [1]

National Health and medical Research Council

Address [1]

Level 5, 20 Allara Street
Canberra ACT 2601

Country [1]

Australia

Primary sponsor type

University

Name

Australian and New Zealand Intensive Care Research Centre

Address

Department of Epidemiology and Preventive Medicine Monash University, Level 6 The Alfred Centre 99 Commercial Road Melbourne Vic 3004

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Other collaborator category [1]

Government body

Name [1]

Victorian Neurotrauma Initiative (VNI)

Address [1]

Level 6, 60 Brougham Street
Geelong Vic 3220

Country [1]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Alfred Hospital Ethics Committee

Ethics committee address [1]

Research & Ethics Unit
2nd Fl, East Block
The Alfred Hospital
Commercial Road
Melbourne Vic 3004

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

06/05/2009

Approval date [1]

10/06/2009

Ethics approval number [1]

09/156

Summary

Brief summary

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).

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Prof Rinaldo Bellomo

Address

Austin Hospital, 145 Studley Road, Heidelberg Vic 3084

Country

Australia

Phone

+61 3 94965992

Fax

rinaldo.bellomo@austin.org.au

Contact person for public queries

Name

Lorraine Little

Address

Department of Epidemiology and Preventive Medicine, Monash University Level 6, The Alfred Centre, 99 Commercial Road Melbourne Vic 3004

Country

Australia

Phone

+61 3 9903 0513

Fax

+61 3 9903 0071

lorraine.little@monash.edu

Contact person for scientific queries

Name

Professor Rinaldo Bellomo

Address

Austin Hospital
145 Studley Road
Heidelberg Vic 3084

Country

Australia

Phone

+61 3 9496 5992

Fax

+61 3 9496 3932

Rinaldo.BELLOMO@austin.org.au

No information has been provided regarding IPD availability

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	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.	2014	https://dx.doi.org/10.1186/1745-6215-15-501
Embase	Erythropoietin in traumatic brain injury: Study protocol for a randomised controlled trial.	2015	https://dx.doi.org/10.1186/s13063-014-0528-6
Embase	Erythropoietin in patients with traumatic brain injury and extracranial injury - A post hoc analysis of the erythropoietin traumatic brain injury trial.	2017	https://dx.doi.org/10.1097/TA.0000000000001594
Embase	Cause and Timing of Death and Subgroup Differential Effects of Erythropoietin in the EPO-TBI Study.	2018	https://dx.doi.org/10.1089/neu.2017.5135
Embase	Erythropoietin in traumatic brain injury associated acute kidney injury: A randomized controlled trial.	2019	https://dx.doi.org/10.1111/aas.13244
Embase	Recent Advances in Modified Brain-Targeting Drug Delivery Systems for Erythropoietin.	2023	https://dx.doi.org/10.1002/adtp.202200326

N.B. These documents automatically identified may not have been verified by the study sponsor.

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