AnemiaPhase 2/3NCT00313716
Effects of Erythropoietin on Cerebral Vascular Dysfunction and Anemia in Traumatic Brain Injury
A Phase 2/3 study testing recombinant human erythropoietin, rhEpo in people with Anemia and Traumatic Brain Injury, run by Claudia Sue Robertson at 1 site in United States.
Trial summary
The purpose of this study is to determine the effect of early administration of recombinant human erythropoietin on long-term neurological outcome after severe traumatic brain injury. Read more about this study
- Who is it for?
- Ages 15 years and older
- Conditions the study is for
- Anemia, Traumatic Brain Injury
- What is being tested?
- recombinant human erythropoietin, rhEpo
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 200 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2006to Mar 2013
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 15 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Blunt trauma mechanism of brain injury
- Glasgow Coma Score - motor component ≤ 5 (not following commands) on the post-resuscitation neurologic exam
- Available for enrollment and administration of study drug within 6 hours of injury
Who cannot join
- Penetrating trauma (i.e. gun shot wounds)
- Glasgow Coma Score = 3 and bilateral fixed and dilated pupils
- Abbreviated Injury Scale score > 5 for any body part except brain
- Severe pre-existing chronic disease
- Uncontrolled hypertension, defined as mean arterial pressure > 130mmHg despite antihypertensive treatment
- Known hypersensitivity to mammalian cell-derived products or human albumin
- Currently taking anticoagulants
Trial locations and contacts
1 site in 1 country.
United States1 site
Baylor College of Medicine, Ben Taub General Hospital
Houston, Texas, 77030
About this study
The purpose of this study is to determine the effect of early administration of recombinant human erythropoietin on long-term neurological outcome after severe traumatic brain injury.
Read the detailed description
Traumatic brain injury (TBI) causes a spectrum of cerebrovascular dysfunction, ranging from impaired pressure autoregulation to severe global ischemia (inadequate blood flow). Pressure autoregulation is the ability of an organ to maintain a constant blood flow despite changes in perfusion pressure. Impaired pressure autoregulation causes TBI patients to be more vulnerable to secondary ischemic attacks.
Erythropoietin (Epo) is a substance that is normally made by the kidneys and stimulates the production of red blood cells. It is usually given to patients to treat anemia. Scientists recently discovered that Epo also is made in the brain after injury. In animal models of TBI, the brain's production of Epo has numerous protective effects, including reducing inflammation in the brain, reducing death of brain cells, and improving blood flow to the brain. In the laboratory, the effects of this naturally-occurring, protective agent can be enhanced by giving additional amounts intravenously. Because Epo may have beneficial effects for both the injured brain and anemia, scientists are studying the effects of giving Epo to patients with severe TBI.
The primary objective of this randomized, placebo-controlled study is to determine the effect of early administration of recombinant human Epo (rhEpo), on long-term neurological outcome in patients with severe TBI. The researchers also will examine the effects of rhEpo administration on the cerebrovascular system, hemoglobin concentration, brain oxygenation, the need for blood transfusion, and on systemic complications.
This study consists of 2 parts: 1) a treatment phase, and 2) a monitoring phase. In the treatment phase, participants will be randomly assigned to 1 of 4 groups: a low or high dose rhEPO treatment group or low or high dose placebo group (control group). All other aspects of treatment during the acute post-injury phase will follow the standard treatment protocol for individuals with severe TBI. Generally the treatment phase lasts 1-2 weeks or the amount of time that is required for patients to receive treatment of their TBIs in the ICU (intensive care unit). The monitoring part of the study (which includes recording information from tests performed as part of the standard TBI treatment, as well as some additional tests performed especially for the study) lasts for up to 6 months after the TBI.
Information learned in this study may lead to knowledge about whether rhEpo improves outcomes after TBI and about the optimal hemoglobin concentration to maintain in patients with TBI.
- Conditions
- Anemia, Traumatic Brain Injury
- Being tested
- recombinant human erythropoietin, rhEpo, placebo
- Keywords
- anemia, traumatic brain injury, recombinant human erythropoietin, rhEpo, erythropoietin, TBI, Epo
- Medical subject headings
- Anemia, Brain Injuries, Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
recombinant human erythropoietin, rhEpoDrug
The study design is 2x2 factorial with randomization to erythropoietin or placebo and to transfusion trigger 10 gm/dl or 7 g/dl. Erythropoietin or placebo was initially dosed daily for 3 days and then weekly for 2 more weeks (first 74 patients, Epo1 dosing regimen), and then the 24- and 48-hour doses were stopped for the remainder of the patients (remaining 126 patients, Epo2 dosing regimen).
placeboOther
an inactive substance
| Study group | Role | What they receive |
|---|---|---|
| Epo1 and TT10 | Active comparator | recombinant human erythropoietin, rhEpo administration (500 IU/kg within 6 hrs of injury, at 24 and 48 hrs after injury, and at 9 and 16 days after injury) and hemoglobin transfusion trigger of 10gm/dl Receives: Drug: recombinant human erythropoietin, rhEpo |
| Epo1 and TT7 | Active comparator | recombinant human erythropoietin, rhEpo administration (500 IU/kg within 6 hrs of injury, at 24 and 48 hrs after injury, and at 9 and 16 days after injury) and hemoglobin transfusion trigger 7gm/dl Receives: Drug: recombinant human erythropoietin, rhEpo |
| Epo2 and TT10 | Active comparator | recombinant human erythropoietin, rhEpo administration (500 IU/kg within 6 hrs of injury, and at 9 and 16 days after injury) and hemoglobin transfusion trigger 10gm/dl Receives: Drug: recombinant human erythropoietin, rhEpo |
| Epo2 and TT7 | Active comparator | recombinant human erythropoietin, rhEpo administration (500 IU/kg within 6 hrs of injury, and at 9 and 16 days after injury) and hemoglobin transfusion trigger 7gm/dl Receives: Drug: recombinant human erythropoietin, rhEpo |
| Placebo and TT10 | Placebo comparator | Placebo administration and transfusion threshold 10 gm/dl Receives: Other: placebo |
| Placebo and TT7 | Placebo comparator | Placebo administration and transfusion threshold 7 gm/dl Receives: Other: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Glasgow Outcome Scale
Dichotomized to favorable outcome (good recovery or moderate disability) or to unfavorable outcome (severe disability or vegetative or dead)
Measured: at 6 months after injury
Secondary outcomes (4)
Disability Rating Scale
Disability rating scale was a secondary outcome measure for the transfusion threshold analysis. Disability rating scale ranges from 0 to 30, with 30 indicating death and 0 indicating return to normal status.
Measured: at 6 months
Mortality Rate
mortality rate was a secondary outcome measure for the Epo randomization, and a primary safety outcome measure for the transfusion threshold randomization
Measured: up to 6 months after injury
Incidence of Adult Respiratory Distress Syndrome (ARDS)
development of ARDS was a primary safety outcome for the transfusion threshold randomization
Measured: within 30 days after injury
Incidence of Infection
occurrence of infection was a primary safety outcome for the transfusion threshold randomization
Measured: within 30 days after injury
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Apr 2006 (estimated)
- Study startApr 2006
- Primary completionMar 2013
- Study completionMar 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for AnemiaStudies 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 200 participants (actual)
Sponsor and investigators
- Lead sponsor
- Claudia Sue Robertson
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Claudia Sue Robertson, Baylor College of Medicine
- Investigators
- Claudia Robertson, MD, Principal investigator, Professor, Department of Neurosurgery, Baylor College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00313716
- Sponsor's protocol ID
- P01NS038660
- Other IDs
- P01NS038660
- Status last verified
- Sep 2014
- First submitted
- 10 Apr 2006
- Last updated
- 10 Sep 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Robertson CS, Hannay HJ, Yamal JM, Gopinath S, Goodman JC, Tilley BC; Epo Severe TBI Trial Investigators; Baldwin A, Rivera Lara L, Saucedo-Crespo H, Ahmed O, Sadasivan S, Ponce L, Cruz-Navarro J, Shahin H, Aisiku IP, Doshi P, Valadka A, Neipert L, Waguspack JM, Rubin ML, Benoit JS, Swank P. Effect of erythropoietin and transfusion threshold on neurological recovery after traumatic brain injury: a randomized clinical trial. JAMA. 2014 Jul 2;312(1):36-47. doi: 10.1001/jama.2014.6490.
PubMed 25058216Aisiku IP, Yamal JM, Doshi P, Benoit JS, Gopinath S, Goodman JC, Robertson CS. Plasma cytokines IL-6, IL-8, and IL-10 are associated with the development of acute respiratory distress syndrome in patients with severe traumatic brain injury. Crit Care. 2016 Sep 15;20:288. doi: 10.1186/s13054-016-1470-7.
PubMed 27630085Yamal JM, Benoit JS, Doshi P, Rubin ML, Tilley BC, Hannay HJ, Robertson CS. Association of transfusion red blood cell storage age and blood oxygenation, long-term neurologic outcome, and mortality in traumatic brain injury. J Trauma Acute Care Surg. 2015 Nov;79(5):843-9. doi: 10.1097/TA.0000000000000834.
PubMed 26496111Aisiku IP, Yamal JM, Doshi P, Rubin ML, Benoit JS, Hannay J, Tilley BC, Gopinath S, Robertson CS. The incidence of ARDS and associated mortality in severe TBI using the Berlin definition. J Trauma Acute Care Surg. 2016 Feb;80(2):308-12. doi: 10.1097/TA.0000000000000903.
PubMed 26491799Yamal JM, Robertson CS, Rubin ML, Benoit JS, Hannay HJ, Tilley BC. Enrollment of racially/ethnically diverse participants in traumatic brain injury trials: effect of availability of exception from informed consent. Clin Trials. 2014 Apr;11(2):187-94. doi: 10.1177/1740774514522560.
PubMed 24686108
Study at a glance
From the registry record, last updated by the sponsor on 10 Sep 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Erythropoietin on Cerebral Vascular Dysfunction and Anemia in Traumatic Brain Injury
- ClinicalTrials.gov ID
- NCT00313716
- Acronym / sponsor ID
- P01NS038660
- Conditions
- Anemia, Traumatic Brain Injury
- Keywords
- anemia, traumatic brain injury, recombinant human erythropoietin, rhEpo, erythropoietin, TBI, Epo
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 200 participants (actual)
- Lead sponsor
- Claudia Sue RobertsonUniversity, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS)
- Study start
- Apr 2006
- Primary completion
- Mar 2013 (actual)
- Study completion
- Mar 2013 (actual)
- First posted
- 12 Apr 2006 (estimated)
- Results
- Posted 10 Sep 2014
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 determine the effect of early administration of recombinant human erythropoietin on long-term neurological outcome after severe traumatic brain injury.
Detailed description
Traumatic brain injury (TBI) causes a spectrum of cerebrovascular dysfunction, ranging from impaired pressure autoregulation to severe global ischemia (inadequate blood flow). Pressure autoregulation is the ability of an organ to maintain a constant blood flow despite changes in perfusion pressure. Impaired pressure autoregulation causes TBI patients to be more vulnerable to secondary ischemic attacks.
Erythropoietin (Epo) is a substance that is normally made by the kidneys and stimulates the production of red blood cells. It is usually given to patients to treat anemia. Scientists recently discovered that Epo also is made in the brain after injury. In animal models of TBI, the brain's production of Epo has numerous protective effects, including reducing inflammation in the brain, reducing death of brain cells, and improving blood flow to the brain. In the laboratory, the effects of this naturally-occurring, protective agent can be enhanced by giving additional amounts intravenously. Because Epo may have beneficial effects for both the injured brain and anemia, scientists are studying the effects of giving Epo to patients with severe TBI.
The primary objective of this randomized, placebo-controlled study is to determine the effect of early administration of recombinant human Epo (rhEpo), on long-term neurological outcome in patients with severe TBI. The researchers also will examine the effects of rhEpo administration on the cerebrovascular system, hemoglobin concentration, brain oxygenation, the need for blood transfusion, and on systemic complications.
This study consists of 2 parts: 1) a treatment phase, and 2) a monitoring phase. In the treatment phase, participants will be randomly assigned to 1 of 4 groups: a low or high dose rhEPO treatment group or low or high dose placebo group (control group). All other aspects of treatment during the acute post-injury phase will follow the standard treatment protocol for individuals with severe TBI. Generally the treatment phase lasts 1-2 weeks or the amount of time that is required for patients to receive treatment of their TBIs in the ICU (intensive care unit). The monitoring part of the study (which includes recording information from tests performed as part of the standard TBI treatment, as well as some additional tests performed especially for the study) lasts for up to 6 months after the TBI.
Information learned in this study may lead to knowledge about whether rhEpo improves outcomes after TBI and about the optimal hemoglobin concentration to maintain in patients with TBI.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Epo1 and TT10 | Active comparator | Drug: recombinant human erythropoietin, rhEporecombinant human erythropoietin, rhEpo administration (500 IU/kg within 6 hrs of injury, at 24 and 48 hrs after injury, and at 9 and 16 days after injury) and hemoglobin transfusion trigger of 10gm/dl |
| Epo1 and TT7 | Active comparator | Drug: recombinant human erythropoietin, rhEporecombinant human erythropoietin, rhEpo administration (500 IU/kg within 6 hrs of injury, at 24 and 48 hrs after injury, and at 9 and 16 days after injury) and hemoglobin transfusion trigger 7gm/dl |
| Epo2 and TT10 | Active comparator | Drug: recombinant human erythropoietin, rhEporecombinant human erythropoietin, rhEpo administration (500 IU/kg within 6 hrs of injury, and at 9 and 16 days after injury) and hemoglobin transfusion trigger 10gm/dl |
| Epo2 and TT7 | Active comparator | Drug: recombinant human erythropoietin, rhEporecombinant human erythropoietin, rhEpo administration (500 IU/kg within 6 hrs of injury, and at 9 and 16 days after injury) and hemoglobin transfusion trigger 7gm/dl |
| Placebo and TT10 | Placebo comparator | Other: placeboPlacebo administration and transfusion threshold 10 gm/dl |
| Placebo and TT7 | Placebo comparator | Other: placeboPlacebo administration and transfusion threshold 7 gm/dl |
Who may qualify
- Ages
- 15 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- Blunt trauma mechanism of brain injury
- Glasgow Coma Score - motor component ≤ 5 (not following commands) on the post-resuscitation neurologic exam
- Available for enrollment and administration of study drug within 6 hours of injury
Key exclusion criteria (7 listed)
- Penetrating trauma (i.e. gun shot wounds)
- Glasgow Coma Score = 3 and bilateral fixed and dilated pupils
- Abbreviated Injury Scale score > 5 for any body part except brain
- Severe pre-existing chronic disease
- Uncontrolled hypertension, defined as mean arterial pressure > 130mmHg despite antihypertensive treatment
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 |
|---|---|---|
| recombinant human erythropoietin, rhEpoThe study design is 2x2 factorial with randomization to erythropoietin or placebo and to transfusion trigger 10 gm/dl or 7 g/dl. Erythropoietin or placebo was initially dosed daily for 3 days and then weekly for 2 more weeks (first 74 patients, Epo1 dosing regimen), and then the 24- and 48-hour doses were stopped for the remainder of the patients (remaining 126 patients, Epo2 dosing regimen). | Drug | Epo1 and TT10, Epo1 and TT7, Epo2 and TT10, Epo2 and TT7 |
| placeboan inactive substance | Other | Placebo and TT10, Placebo and TT7 |
Primary outcome
Glasgow Outcome Scale
Time frame: at 6 months after injury
Dichotomized to favorable outcome (good recovery or moderate disability) or to unfavorable outcome (severe disability or vegetative or dead)
4 secondary outcomes
Disability Rating Scale
Time frame: at 6 months
Mortality Rate
Time frame: up to 6 months after injury
Incidence of Adult Respiratory Distress Syndrome (ARDS)
Time frame: within 30 days after injury
Incidence of Infection
Time frame: within 30 days after injury
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Sep 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 25058216Robertson CS, Hannay HJ, Yamal JM, Gopinath S, Goodman JC, Tilley BC; Epo Severe TBI Trial Investigators; Baldwin A, Rivera Lara L, Saucedo-Crespo H, Ahmed O, Sadasivan S, Ponce L, Cruz-Navarro J, Shahin H, Aisiku IP, Doshi P, Valadka A, Neipert L, Waguspack JM, Rubin ML, Benoit JS, Swank P. Effect of erythropoietin and transfusion threshold on neurological recovery after traumatic brain injury: a randomized clinical trial. JAMA. 2014 Jul 2;312(1):36-47. doi: 10.1001/jama.2014.6490.
- Derived from this study: PubMed 27630085Aisiku IP, Yamal JM, Doshi P, Benoit JS, Gopinath S, Goodman JC, Robertson CS. Plasma cytokines IL-6, IL-8, and IL-10 are associated with the development of acute respiratory distress syndrome in patients with severe traumatic brain injury. Crit Care. 2016 Sep 15;20:288. doi: 10.1186/s13054-016-1470-7.
- Derived from this study: PubMed 26496111Yamal JM, Benoit JS, Doshi P, Rubin ML, Tilley BC, Hannay HJ, Robertson CS. Association of transfusion red blood cell storage age and blood oxygenation, long-term neurologic outcome, and mortality in traumatic brain injury. J Trauma Acute Care Surg. 2015 Nov;79(5):843-9. doi: 10.1097/TA.0000000000000834.
- Derived from this study: PubMed 26491799Aisiku IP, Yamal JM, Doshi P, Rubin ML, Benoit JS, Hannay J, Tilley BC, Gopinath S, Robertson CS. The incidence of ARDS and associated mortality in severe TBI using the Berlin definition. J Trauma Acute Care Surg. 2016 Feb;80(2):308-12. doi: 10.1097/TA.0000000000000903.
- Derived from this study: PubMed 24686108Yamal JM, Robertson CS, Rubin ML, Benoit JS, Hannay HJ, Tilley BC. Enrollment of racially/ethnically diverse participants in traumatic brain injury trials: effect of availability of exception from informed consent. Clin Trials. 2014 Apr;11(2):187-94. doi: 10.1177/1740774514522560.
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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.
Claudia Robertson, MD principal investigator
Professor, Department of Neurosurgery, Baylor College of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing recombinant human erythropoietin, rhEpo in people with Anemia and Traumatic Brain Injury, run by Claudia Sue Robertson at 1 site in United States.
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 3 inclusion and 7 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 10 Sep 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 combined 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.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Sep 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Glasgow Outcome Scale (time frame: at 6 months after injury). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00313716, which also lists 5 linked publications.
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 10 Sep 2014.