Erythropoietin in Traumatic Brain Injury (EPO-TBI)

NCT00987454 | Completed Phase 3 DMC

• 1 other identifier: ANZIC-RC/RB002
• Study Type: interventional
• Target: 606
• Locations: 7 countries
• Sites: 28

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.

Conditions

Traumatic Brain Injury

Outcome Measures

Primary Outcomes (1)

• Combined proportion of unfavourable neurological outcomes at 6 months: severe disability (defined as GOSE scores 2-4) or death (GOSE score 1).

  6 months

Secondary Outcomes (7)

• 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

  6 months

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

  6 months

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

  6 months

• Mortality at 6 months

  6 months

• Rate of proximal deep venous thrombosis detected during screening by compression Doppler ultrasound

  21 days

Study Arms (2)

Erythropoietin

ACTIVE COMPARATOR

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.

Drug: Epoetin Alfa

Placebo

PLACEBO COMPARATOR

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.

Drug: Sodium Chloride 0.9%

Interventions

Epoetin Alfa DRUG

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

Also known as: Eprex

Erythropoietin

Sodium Chloride 0.9% DRUG

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

Also known as: Normal Saline

Placebo

Eligibility Criteria

• Age: 15 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Australian and New Zealand Intensive Care Research Centre: lead
• National Health and Medical Research Council, Australia: collaborator
• Australian and New Zealand Intensive Care Society Clinical Trials Group: collaborator
• Monash University: collaborator

Study Sites (28)

Canberra Hospital

Canberra, Australian Capital Territory, 2605, Australia

Location

Royal Prince Alfred Hospital

Camperdown, New South Wales, 2050, Australia

Location

St Vincent's Hospital Sydney

Darlinghurst, New South Wales, 2010, Australia

Location

Liverpool Hospital

Liverpool, New South Wales, 2170, Australia

Location

John Hunter Hospital

Newcastle, New South Wales, 2305, Australia

Location

Royal North Shore Hospital

St Leonards, New South Wales, 2065, Australia

Location

Westmead Hospital

Westmead, New South Wales, 2145, Australia

Location

Gold Coast University Hospital

Southport, Queensland, 4215, Australia

Location

The Townsville Hospital

Townsville, Queensland, 4814, Australia

Location

Royal Adelaide Hosptial

Adelaide, South Australia, 5000, Australia

Location

Royal Hobart Hospital

Hobart, Tasmania, 7000, Australia

Location

The Royal Melbourne Hospital

Melbourne, Victoria, 3050, Australia

Location

The Alfred Hospital

Melbourne, Victoria, 3181, Australia

Location

Royal Perth Hospital

Perth, Western Australia, Australia

Location

Helsinki University Central Hospital

Helsinki, 00029, Finland

Location

Kuopio University Hospital

Kuopio, 70211, Finland

Location

Hôpital Michallon

Grenoble, 38 043, France

Location

Hôpital universitaire Caremeau

Nîmes, 30029, France

Location

Hôpital Lariboisière

Paris, 75 475, France

Location

Hôpital de Bicêtre

Paris, 94275, France

Location

CHU de Rouen

Rouen, 76 031, France

Location

Johannes Gutenberg-Universtität

Mainz, D-55131, Germany

Location

Beaumont Hospital

Dublin, 9, Ireland

Location

Auckland City Hospital

Auckland, North Island, 1023, New Zealand

Location

Wellington Regional Hospital

Wellington, North Island, 6021, New Zealand

Location

Christchurch Hospital

Christchurch, South Island, 8011, New Zealand

Location

Dunedin Hospital

Dunedin, New Zealand

Location

King Fahad National Guard Hospital

Riyadh, 22490, Saudi Arabia

Location

Related Publications (7)

• 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.

  PMID: 39301879 DERIVED

• 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.

  PMID: 33566466 DERIVED

• 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.

  PMID: 30132785 DERIVED

• 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.

  PMID: 26452709 DERIVED

• 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.

  PMID: 25884605 DERIVED

• 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.

  PMID: 25528574 DERIVED

• 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.

  PMID: 21675055 DERIVED

MeSH Terms

Conditions

Brain Injuries, Traumatic

Interventions

Epoetin Alfa; Sodium Chloride; Saline Solution

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Erythropoietin; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Alistair D Nichol, MD

  Monash University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 29, 2009
• First Posted: October 1, 2009
• Study Start: May 1, 2010
• Primary Completion: May 1, 2015
• Study Completion: May 1, 2015
• Last Updated: July 26, 2016

Record last verified: 2016-07

Locations

FR (5); AU (14); IE (1); DE (1); NZ (4); SA (1); FI (2)