Traumatic Brain InjuryPhase 2NCT00375869
Safety of Darbepoetin Alfa Treatment in Patients With Severe Traumatic Brain Injury
A Phase 2 study testing Darbeopoetin in people with Traumatic Brain Injury, run by Royal Alexandra Hospital at 2 sites in Canada.
Trial summary
The purpose of this study is to see if the treatment of severely brain injured patients with darbepoetin (a long acting form of erythropoietin) will be safe, and will reduce brain damage by decreasing harmful levels of chemicals in the brain. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Traumatic Brain Injury
- What is being tested?
- Darbeopoetin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 10 participants
- Where
- 2 sitesCanada
- Study dates
- Nov 2006to Dec 2009
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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
Trial locations and contacts
2 sites in 1 country.
Canada2 sites
Royal Alexandra Hospital
Edmonton, Alberta, T5H 3V9
University of Alberta Hospital
Edmonton, Alberta, T6G 2B7
About this study
Official title: A Prospective Randomized Placebo Controlled Study of the Efficacy and Safety of Darbepoetin Alfa Treatment in Patients With Severe Traumatic Brain Injury
The purpose of this study is to see if the treatment of severely brain injured patients with darbepoetin (a long acting form of erythropoietin) will be safe, and will reduce brain damage by decreasing harmful levels of chemicals in the brain.
Read the 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.
- Conditions
- Traumatic Brain Injury
- Being tested
- Darbeopoetin, Normal Saline (Placebo)
- Keywords
- Neuroprotection, neuron specific enolase, CSF glutamate levels, Darbepoetin Alfa
- Medical subject headings
- Brain Injuries, Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DarbeopoetinDrug
Also called ARANESP
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.
Normal Saline (Placebo)Drug
Also called 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.
| Study group | Role | What they receive |
|---|---|---|
| Darbopoeitin | Active comparator | 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. Receives: Drug: Darbeopoetin |
| Normal Saline (Placebo) | Placebo comparator | 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. Receives: Drug: Normal Saline (Placebo) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Neuron-specific serum enolase, CSF glutamate and CSF S100B levels in patients receiving darbepoetin compared to placebo
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
Measured: over 96 hours
Secondary outcomes (1)
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.
Measured: day 28 and 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Sep 2006 (estimated)
- Study startNov 2006
- Primary completionDec 2009
- Study completionDec 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Traumatic Brain InjuryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Royal Alexandra Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- University of Alberta
- Responsible party
- Principal investigator, Demetrios J. Kutsogiannis, Royal Alexandra Hospital
- Investigators
- Demetrios J. Kutsogiannis, MD MHS FRCPC, Principal investigator, Division of Critical Care Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00375869
- Sponsor's protocol ID
- TBI2006
- Status last verified
- Mar 2012
- First submitted
- 12 Sep 2006
- Last updated
- 5 Mar 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective Randomized Placebo Controlled Study of the Efficacy and Safety of Darbepoetin Alfa Treatment in Patients With Severe Traumatic Brain Injury
- ClinicalTrials.gov ID
- NCT00375869
- Acronym / sponsor ID
- TBI2006
- Conditions
- Traumatic Brain Injury
- Keywords
- Neuroprotection, neuron specific enolase, CSF glutamate levels, Darbepoetin Alfa
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Royal Alexandra HospitalUniversity, hospital or other
- Collaborators
- University of Alberta
- Study start
- Nov 2006
- Primary completion
- Dec 2009 (actual)
- Study completion
- Dec 2009 (actual)
- First posted
- 13 Sep 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to see if the treatment of severely brain injured patients with darbepoetin (a long acting form of erythropoietin) will be safe, and will reduce brain damage by decreasing harmful levels of chemicals in the brain.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Darbopoeitin | Active comparator | Drug: DarbeopoetinThe 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. |
| Normal Saline (Placebo) | Placebo comparator | Drug: 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. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DarbeopoetinAlso: ARANESPThe 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. | Drug | Darbopoeitin |
| Normal Saline (Placebo)Also: PlaceboThe 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. | Drug | Normal Saline (Placebo) |
Primary outcome
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
1 secondary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2012.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Demetrios J. Kutsogiannis, MD MHS FRCPC principal investigator
Division of Critical Care Medicine
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Darbeopoetin in people with Traumatic Brain Injury, run by Royal Alexandra Hospital at 2 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Mar 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Neuron-specific serum enolase, CSF glutamate and CSF S100B levels in patients receiving darbepoetin compared to placebo (time frame: over 96 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Mar 2012.