- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00375869
Safety of Darbepoetin Alfa Treatment in Patients With Severe Traumatic Brain Injury
A Prospective Randomized Placebo Controlled Study of the Efficacy and Safety of Darbepoetin Alfa Treatment in Patients With Severe Traumatic Brain Injury
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Traumatic brain injury (TBI) is a common neurosurgical problem with a high morbidity and mortality. Studies interested in defining possible therapeutic targets in TBI have led to an appreciation of two phases of injury. These phases are referred to as primary and secondary TBI. The primary injury encompasses the immediate insult, diffuse axonal injury, hemorrhage, contusion, and primary ischemia. The secondary injury evolves over the post-traumatic period and is due to a combination of vasogenic and cytotoxic edema resulting from several processes including; glutamate excitotoxicity, disturbance of ionic homeostasis, lipid peroxidation, generation of nitric oxide (NO) and free radicals, and release of inflammatory regulators such as bradykinin and eicosanoids. It has long been recognized that one of the most important factors in the secondary injury process is the indiscriminate release of the excitatory neurotransmitter glutamate from neurons and glia. Glutamate excitotoxicity leads to substantial intraneuronal release of calcium which in turn mediates the activation of phospholipases which generate arachadonic acid, the activation of proteases, and the activation of NO, all of which cause neuronal membrane disruption and loss of ionic equilibrium. Receptors for erythropoietin (EPOr) are distributed throughout the brain and studies have demonstrated that these receptors are not only important in the process of development but also in neuroprotection. Treatment with erythropoietin (EPO) protects neurons in models of ischemic and traumatic degenerative damage due to exocitotoxins and consequent generation of free radicals including NO. EPOr activation also prevents the indiscriminate exocytosis of glutamate in a model of chemically induced ischemia on neurons of rat hippocampus.
The hypothesis of this study is that treatment of severely brain injured patients with darbepoetin alfa (Aranesp®) will be safe and reduce the cerebrospinal fluid (CSF) levels of glutamate within a 96 hour period after traumatic brain injury. This effect is potentially mediated through the activation of EPO receptors whose activation prevents the exocytosis of glutamate, a known neurocytotoxin, into CSF.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Alberta
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Edmonton, Alberta, Canada, T6G 2B7
- University of Alberta Hospital
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Edmonton, Alberta, Canada, T5H 3V9
- Royal Alexandra Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Age 18-70 inclusive.
- Admitted to ICU with a TBI and a GCS ≤ 8 with a motor score < 6.
- Patient must have a functioning external ventricular drain in place for intracranial pressure (ICP) monitoring.
- Completion of informed consent by the next-of-kin or legal guardian.
- Randomization within 12 hours of initial triage by medical or paramedical staff.
- Abnormal CT of the brain.
Exclusion Criteria:
- Pregnancy
- Cardiac arrest during the current hospital admission.
- Bilateral non-reactive dilated pupils at the time of randomization.
- A history of renal failure, NYHA class IV congestive heart failure, or recent myocardial infarction (within 6 months).
- A history of primary or secondary polycythemia.
- Previous adverse reactions to rhEPO or darbepoetin.
- Previous history of seizure disorder.
- Recent history (within the past 3 months) of significant uncontrolled hypertension defined as SBP > 200 mm Hg or DBP > 110 mmHg.
- Patients involved in other clinical investigations involving therapeutic interventions
- Hemoglobin ≥150 g/L in females
- Hemoglobin ≥160g/L in males
- Past history of thrombotic events
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Darbopoeitin
The treatment group, comprised of ten patients, will receive an intravenous dose of 200 mcg (1 ml) of darbepoetin (Aranesp®).
Patients will be randomly assigned to either the treatment group, or the control group in a 2:1 ratio.
The treatment group will be given 200 mcg of darbepoetin intravenously.
The control group will be given a matching placebo of 1 mL of normal saline.
|
The treatment group, comprised of ten patients, will receive an intravenous dose of 200 mcg (1 ml) of darbepoetin (Aranesp®).
Patients will be randomly assigned to either the treatment group, or the control group in a 2:1 ratio.
The treatment group will be given 200 mcg of darbepoetin intravenously.
The control group will be given a matching placebo of 1 mL of normal saline.
Other Names:
|
Placebo Comparator: Normal Saline (Placebo)
The treatment group, comprised of ten patients, will receive an intravenous dose of 200 mcg (1 ml) of darbepoetin (Aranesp®).
Patients will be randomly assigned to either the treatment group, or the control group in a 2:1 ratio.
The treatment group will be given 200 mcg of darbepoetin intravenously.
The control group will be given a matching placebo of 1 mL of normal saline.
|
The treatment group, comprised of ten patients, will receive an intravenous dose of 200 mcg (1 ml) of darbepoetin (Aranesp®).
Patients will be randomly assigned to either the treatment group, or the control group in a 2:1 ratio.
The treatment group will be given 200 mcg of darbepoetin intravenously.
The control group will be given a matching placebo of 1 mL of normal saline.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Neuron-specific serum enolase, CSF glutamate and CSF S100B levels in patients receiving darbepoetin compared to placebo
Time Frame: over 96 hours
|
The primary outcome measures include Neuron-specific serum enolase, CSF glutamate and CSF S100B levels in patients receiving darbepoetin compared to placebo over a 96 hour period and ICP levels in patients receiving darbepoetin compared to placebo over a 96 hour period
|
over 96 hours
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Secondary outcome measures include ICU and hospital length of stay, GCS at ICU discharge, survival status, location after ICU and hospital discharge. GCS will be evaluated at day 28 and 1 year.
Time Frame: day 28 and 1 year
|
day 28 and 1 year
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Demetrios J. Kutsogiannis, MD MHS FRCPC, Division of Critical Care Medicine
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- TBI2006
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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