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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00987454




Registration number
NCT00987454
Ethics application status
Date submitted
29/09/2009
Date registered
1/10/2009
Date last updated
26/07/2016

Titles & IDs
Public title
Erythropoietin in Traumatic Brain Injury (EPO-TBI)
Scientific title
A Randomised, Placebo-controlled Trial of Erythropoietin in ICU Patients With Traumatic Brain Injury
Secondary ID [1] 0 0
ANZIC-RC/RB002
Universal Trial Number (UTN)
Trial acronym
EPO-TBI
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Traumatic Brain Injury 0 0
Condition category
Condition code
Injuries and Accidents 0 0 0 0
Other injuries and accidents
Neurological 0 0 0 0
Other neurological disorders
Skin 0 0 0 0
Other skin conditions

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Epoetin Alfa
Treatment: Drugs - Sodium Chloride 0.9%

Active comparator: 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.

Placebo comparator: 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.


Treatment: Drugs: Epoetin Alfa
40,000 IU given as subcutaneous injection weekly up to 3 doses

Treatment: Drugs: Sodium Chloride 0.9%
1 m/L given as subcutaneous injection weekly up to 3 doses
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Combined proportion of unfavourable neurological outcomes at 6 months: severe disability (defined as GOSE scores 2-4) or death (GOSE score 1).
Timepoint [1] 0 0
6 months
Secondary outcome [1] 0 0
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
Timepoint [1] 0 0
6 months
Secondary outcome [2] 0 0
Proportion of surviving patients with unfavourable neurological outcome (GOSE 2-4) at 6 months
Timepoint [2] 0 0
6 months
Secondary outcome [3] 0 0
Quality of life assessment (SF-12 and EQ-5D) at 6 months
Timepoint [3] 0 0
6 months
Secondary outcome [4] 0 0
Mortality at 6 months
Timepoint [4] 0 0
6 months
Secondary outcome [5] 0 0
Rate of proximal deep venous thrombosis detected during screening by compression Doppler ultrasound
Timepoint [5] 0 0
21 days
Secondary outcome [6] 0 0
Proportion of patients with composite thrombotic vascular events (DVT, pulmonary embolus, myocardial infarction, cardiac arrest and cerebrovascular events) at 6 months
Timepoint [6] 0 0
6 months
Secondary outcome [7] 0 0
Cost effectiveness analysis at 6 months (based on EQ-5D)
Timepoint [7] 0 0
6 months

Eligibility
Key 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
Minimum age
15 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/05/2010
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/05/2015
Sample size
Target
Accrual to date
Final
606
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,SA,TAS,VIC,WA
Recruitment hospital [1] 0 0
Canberra Hospital - Canberra
Recruitment hospital [2] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [3] 0 0
St Vincent's Hospital Sydney - Darlinghurst
Recruitment hospital [4] 0 0
Liverpool Hospital - Liverpool
Recruitment hospital [5] 0 0
John Hunter Hospital - Newcastle
Recruitment hospital [6] 0 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [7] 0 0
Westmead Hospital - Westmead
Recruitment hospital [8] 0 0
Gold Coast University Hospital - Southport
Recruitment hospital [9] 0 0
The Townsville Hospital - Townsville
Recruitment hospital [10] 0 0
Royal Adelaide Hosptial - Adelaide
Recruitment hospital [11] 0 0
Royal Hobart Hospital - Hobart
Recruitment hospital [12] 0 0
The Royal Melbourne Hospital - Melbourne
Recruitment hospital [13] 0 0
The Alfred Hospital - Melbourne
Recruitment hospital [14] 0 0
Royal Perth Hospital - Perth
Recruitment postcode(s) [1] 0 0
2605 - Canberra
Recruitment postcode(s) [2] 0 0
2050 - Camperdown
Recruitment postcode(s) [3] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [4] 0 0
2170 - Liverpool
Recruitment postcode(s) [5] 0 0
2305 - Newcastle
Recruitment postcode(s) [6] 0 0
2065 - St Leonards
Recruitment postcode(s) [7] 0 0
2145 - Westmead
Recruitment postcode(s) [8] 0 0
4215 - Southport
Recruitment postcode(s) [9] 0 0
4814 - Townsville
Recruitment postcode(s) [10] 0 0
5000 - Adelaide
Recruitment postcode(s) [11] 0 0
7000 - Hobart
Recruitment postcode(s) [12] 0 0
3050 - Melbourne
Recruitment postcode(s) [13] 0 0
3181 - Melbourne
Recruitment postcode(s) [14] 0 0
- Perth
Recruitment outside Australia
Country [1] 0 0
Finland
State/province [1] 0 0
Helsinki
Country [2] 0 0
Finland
State/province [2] 0 0
Kuopio
Country [3] 0 0
France
State/province [3] 0 0
Grenoble
Country [4] 0 0
France
State/province [4] 0 0
Nîmes
Country [5] 0 0
France
State/province [5] 0 0
Paris
Country [6] 0 0
France
State/province [6] 0 0
Rouen
Country [7] 0 0
Germany
State/province [7] 0 0
Mainz
Country [8] 0 0
Ireland
State/province [8] 0 0
Dublin
Country [9] 0 0
New Zealand
State/province [9] 0 0
North Island
Country [10] 0 0
New Zealand
State/province [10] 0 0
South Island
Country [11] 0 0
New Zealand
State/province [11] 0 0
Dunedin
Country [12] 0 0
Saudi Arabia
State/province [12] 0 0
Riyadh

Funding & Sponsors
Primary sponsor type
Other
Name
Australian and New Zealand Intensive Care Research Centre
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
National Health and Medical Research Council, Australia
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Australian and New Zealand Intensive Care Society Clinical Trials Group
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
Monash University
Address [3] 0 0
Country [3] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
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.
Trial website
https://clinicaltrials.gov/study/NCT00987454
Trial related presentations / publications
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.
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.
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.
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.
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Alistair D Nichol, MD
Address 0 0
Monash University
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00987454