Erythropoietin in Traumatic Brain Injury (EPO-TBI)

Traumatic Brain Injury Clinical Trial

— EPO-TBI  

Official title:

A Randomised, Placebo-controlled Trial of Erythropoietin in ICU Patients With Traumatic Brain Injury

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00987454
• Other study ID #: ANZIC-RC/RB002
• Status: Completed
• Phase: Phase 3
• First received: September 29, 2009
• Last updated: July 24, 2016
• Start date: May 2010
• Est. completion date: May 2015

Study information

• Verified date: July 2016
• Source: Australian and New Zealand Intensive Care Research Centre
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: Department of Health and Ageing Therapeutic Goods AdministrationFinland: Finnish Medicines AgencyFrance: National Agency for Medicines and Health Products SafetyGermany: Federal Institute for Drugs and Medical DevicesIreland: Irish Medicines Board
• Study type: Interventional

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 606
• Est. completion date: May 2015
• Est. primary completion date: May 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 15 Years to 65 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain Injuries
• Traumatic Brain Injury
• Wounds and Injuries

Intervention

Drug:
• Epoetin Alfa
40,000 IU given as subcutaneous injection weekly up to 3 doses
• Sodium Chloride 0.9%
1 m/L given as subcutaneous injection weekly up to 3 doses

Locations

Country	Name	City	State
Australia	Royal Adelaide Hosptial	Adelaide	South Australia
Australia	Royal Prince Alfred Hospital	Camperdown	New South Wales
Australia	Canberra Hospital	Canberra	Australian Capital Territory
Australia	St Vincent's Hospital Sydney	Darlinghurst	New South Wales
Australia	Royal Hobart Hospital	Hobart	Tasmania
Australia	Liverpool Hospital	Liverpool	New South Wales
Australia	The Alfred Hospital	Melbourne	Victoria
Australia	The Royal Melbourne Hospital	Melbourne	Victoria
Australia	John Hunter Hospital	Newcastle	New South Wales
Australia	Royal Perth Hospital	Perth	Western Australia
Australia	Gold Coast University Hospital	Southport	Queensland
Australia	Royal North Shore Hospital	St Leonards	New South Wales
Australia	The Townsville Hospital	Townsville	Queensland
Australia	Westmead Hospital	Westmead	New South Wales
Finland	Helsinki University Central Hospital	Helsinki
Finland	Kuopio University Hospital	Kuopio
France	Hôpital Michallon	Grenoble
France	Hôpital universitaire Caremeau	Nîmes
France	Hôpital de Bicêtre	Paris
France	Hôpital Lariboisière	Paris
France	CHU de Rouen	Rouen
Germany	Johannes Gutenberg-Universtität	Mainz
Ireland	Beaumont Hospital	Dublin
New Zealand	Auckland City Hospital	Auckland	North Island
New Zealand	Christchurch Hospital	Christchurch	South Island
New Zealand	Dunedin Hospital	Dunedin
New Zealand	Wellington Regional Hospital	Wellington	North Island
Saudi Arabia	King Fahad National Guard Hospital	Riyadh

Sponsors (4)

Lead Sponsor	Collaborator
Australian and New Zealand Intensive Care Research Centre	Australian and New Zealand Intensive Care Society Clinical Trials Group, Monash University, National Health and Medical Research Council, Australia

Countries where clinical trial is conducted

Australia,  Finland,  France,  Germany,  Ireland,  New Zealand,  Saudi Arabia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Combined proportion of unfavourable neurological outcomes at 6 months: severe disability (defined as GOSE scores 2-4) or death (GOSE score 1).		6 months	No
Secondary	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	No
Secondary	Proportion of surviving patients with unfavourable neurological outcome (GOSE 2-4) at 6 months		6 months	No
Secondary	Quality of life assessment (SF-12 and EQ-5D) at 6 months		6 months	No
Secondary	Mortality at 6 months		6 months	No
Secondary	Rate of proximal deep venous thrombosis detected during screening by compression Doppler ultrasound		21 days	Yes
Secondary	Proportion of patients with composite thrombotic vascular events (DVT, pulmonary embolus, myocardial infarction, cardiac arrest and cerebrovascular events) at 6 months		6 months	Yes
Secondary	Cost effectiveness analysis at 6 months (based on EQ-5D)		6 months	No