Trial Review

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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] 1107 0
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 251899 0
Severe traumatic brain injury 251900 0
Condition category
Condition code
Injuries and Accidents 252073 252073 0 0
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] 241327 0
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] 252970 0
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] 252970 0
6 months after traumatic brain injury
Secondary outcome [1] 257710 0
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] 257710 0
6 months after traumatic brain injury
Secondary outcome [2] 257711 0
Proportion of surviving patients with unfavourable neurological outcome (GOSE 2-4) at 6 months
Timepoint [2] 257711 0
6 months after traumatic brain injury
Secondary outcome [3] 257712 0
Quality of life assessment (SF-12 and EQ-5D) at 6 months
Timepoint [3] 257712 0
6 months after traumatic brain injury
Secondary outcome [4] 257713 0
All-cause mortality assessed via clinical database.
Timepoint [4] 257713 0
6 months after traumatic brain injury
Secondary outcome [5] 257714 0
Rate of proximal deep venous thrombosis (DVT) detected during screening by compression Doppler ultrasound
Timepoint [5] 257714 0
Up to ICU discharge
Secondary outcome [6] 257715 0
Proportion of patients with composite thrombotic vascular events (DVT, Pulmonary Embolism (PE), myocardial infarction, cardiac arrest and cerebrovascular events) at 6 months
Timepoint [6] 257715 0
6 months after traumatic brain injury
Secondary outcome [7] 257717 0
Cost-effectiveness analysis for patients enrolled in the study based on the questionnaire EQ-5D.
Timepoint [7] 257717 0
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?
No
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] 2119 0
2010
Recruitment postcode(s) [2] 2120 0
2050
Recruitment postcode(s) [3] 2118 0
2065
Recruitment postcode(s) [4] 2122 0
2145
Recruitment postcode(s) [5] 2123 0
2170
Recruitment postcode(s) [6] 2116 0
2605
Recruitment postcode(s) [7] 2117 0
2750
Recruitment postcode(s) [8] 2126 0
3050
Recruitment postcode(s) [9] 2127 0
3181
Recruitment postcode(s) [10] 2124 0
4215
Recruitment postcode(s) [11] 2125 0
4814
Recruitment postcode(s) [12] 2128 0
5000
Recruitment postcode(s) [13] 10218 0
6000 - Perth
Recruitment postcode(s) [14] 2129 0
7000
Recruitment outside Australia
Country [1] 2152 0
New Zealand
State/province [1] 2152 0
Auckland
Country [2] 2153 0
New Zealand
State/province [2] 2153 0
Wellington
Country [3] 2154 0
New Zealand
State/province [3] 2154 0
Christchurch
Country [4] 2155 0
Saudi Arabia
State/province [4] 2155 0
Riyadh
Country [5] 7123 0
New Zealand
State/province [5] 7123 0
Dunedin

Funding & Sponsors
Funding source category [1] 243774 0
Government body
Name [1] 243774 0
National Health and medical Research Council
Country [1] 243774 0
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] 237133 0
None
Name [1] 237133 0
Address [1] 237133 0
Country [1] 237133 0
Other collaborator category [1] 878 0
Government body
Name [1] 878 0
Victorian Neurotrauma Initiative (VNI)
Address [1] 878 0
Level 6, 60 Brougham Street
Geelong Vic 3220
Country [1] 878 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 243904 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 243904 0
Research & Ethics Unit
2nd Fl, East Block
The Alfred Hospital
Commercial Road
Melbourne Vic 3004
Ethics committee country [1] 243904 0
Australia
Date submitted for ethics approval [1] 243904 0
06/05/2009
Approval date [1] 243904 0
10/06/2009
Ethics approval number [1] 243904 0
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 30320 0
Prof Rinaldo Bellomo
Address 30320 0
Austin Hospital, 145 Studley Road, Heidelberg Vic 3084
Country 30320 0
Australia
Phone 30320 0
+61 3 94965992
Fax 30320 0
Email 30320 0
rinaldo.bellomo@austin.org.au
Contact person for public queries
Name 13567 0
Ms Lorraine Little
Address 13567 0
Department of Epidemiology and Preventive Medicine, Monash University Level 6, The Alfred Centre, 99 Commercial Road Melbourne Vic 3004
Country 13567 0
Australia
Phone 13567 0
+61 3 9903 0513
Fax 13567 0
+61 3 9903 0071
Email 13567 0
lorraine.little@monash.edu
Contact person for scientific queries
Name 4495 0
Prof Professor Rinaldo Bellomo
Address 4495 0
Austin Hospital
145 Studley Road
Heidelberg Vic 3084
Country 4495 0
Australia
Phone 4495 0
+61 3 9496 5992
Fax 4495 0
+61 3 9496 3932
Email 4495 0
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
SourceTitleYear of PublicationDOI
EmbaseStatistical 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.2014https://dx.doi.org/10.1186/1745-6215-15-501
EmbaseErythropoietin in traumatic brain injury: Study protocol for a randomised controlled trial.2015https://dx.doi.org/10.1186/s13063-014-0528-6
EmbaseErythropoietin in patients with traumatic brain injury and extracranial injury - A post hoc analysis of the erythropoietin traumatic brain injury trial.2017https://dx.doi.org/10.1097/TA.0000000000001594
EmbaseCause and Timing of Death and Subgroup Differential Effects of Erythropoietin in the EPO-TBI Study.2018https://dx.doi.org/10.1089/neu.2017.5135
EmbaseErythropoietin in traumatic brain injury associated acute kidney injury: A randomized controlled trial.2019https://dx.doi.org/10.1111/aas.13244
EmbaseRecent Advances in Modified Brain-Targeting Drug Delivery Systems for Erythropoietin.2023https://dx.doi.org/10.1002/adtp.202200326
N.B. These documents automatically identified may not have been verified by the study sponsor.