Effects of Erythropoietin on Cerebral Vascular Dysfunction and Anemia in Traumatic Brain Injury
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Anemia Traumatic Brain Injury |
Drug: recombinant human erythropoietin, rhEpo Other: placebo |
Phase 2 Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Factorial Assignment Masking: Double Blind (Subject, Investigator, Outcomes Assessor) Primary Purpose: Treatment |
| Official Title: | Effects of Erythropoietin on Cerebral Vascular Dysfunction and Anemia in Traumatic Brain Injury |
- Glasgow Outcome Scale [ Time Frame: at 6 months ] [ Designated as safety issue: No ]
- Disability rating scale [ Time Frame: at 6 months ] [ Designated as safety issue: No ]
- Cerebral blood flow within 12hr [ Time Frame: at 48 hr and 120 hr post-injury ] [ Designated as safety issue: No ]
- Cerebrovascular function (pressure autoregulation, CO2 reactivity) on days 1-10 post-injury [ Time Frame: on days 1-10 post-injury ] [ Designated as safety issue: No ]
- Hemoglobin concentration during ICU stay [ Time Frame: during ICU stay or first 30 days post-injury (whichever comes first) ] [ Designated as safety issue: No ]
- Number of transfusions of packed red blood cells required [ Time Frame: during ICU stay or first 30 days post-injury (whichever comes first) ] [ Designated as safety issue: No ]
- Infection rate [ Time Frame: during the first 30 days post-injury ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 200 |
| Study Start Date: | April 2006 |
| Estimated Study Completion Date: | March 2013 |
| Estimated Primary Completion Date: | March 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Active Comparator: 1
recombinant human erythropoietin (rhEpo) administration and hemoglobin transfusion trigger of 10gm/dl
|
Drug: recombinant human erythropoietin, rhEpo
The study design is 2x2 factorial with randomization to erythropoietin or placebo and to transfusion trigger 10 gm/dl or 7 g/dl.
|
|
Active Comparator: 2
recombinant human erythropoietin (rhEpo) administration and hemoglobin transfusion trigger 7gm/dl
|
Drug: recombinant human erythropoietin, rhEpo
The study design is 2x2 factorial with randomization to erythropoietin or placebo and to transfusion trigger 10 gm/dl or 7 g/dl.
|
|
Active Comparator: 3
placebo administration and hemoglobin transfusion trigger 10gm/dl
|
Other: placebo
an inactive substance
|
|
Active Comparator: 4
placebo administration and hemoglobin transfusion trigger 7gm/dl
|
Other: placebo
an inactive substance
|
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.
Eligibility| Ages Eligible for Study: | 15 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
Contacts and Locations| United States, Texas | |
| Baylor College of Medicine, Ben Taub General Hospital | |
| Houston, Texas, United States, 77030 | |
| Principal Investigator: | Claudia Robertson, MD | Professor, Department of Neurosurgery, Baylor College of Medicine |
More Information
No publications provided
| Responsible Party: | Claudia Sue Robertson, Professor, Department of Neurosurgery, Baylor College of Medicine |
| ClinicalTrials.gov Identifier: | NCT00313716 History of Changes |
| Other Study ID Numbers: | P01NS38660, P01NS038660 |
| Study First Received: | April 10, 2006 |
| Last Updated: | February 1, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by Baylor College of Medicine:
|
anemia traumatic brain injury recombinant human erythropoietin rhEpo |
erythropoietin TBI Epo |
Additional relevant MeSH terms:
|
Anemia Brain Injuries Hematologic Diseases Brain Diseases Central Nervous System Diseases Nervous System Diseases Craniocerebral Trauma |
Trauma, Nervous System Wounds and Injuries Epoetin Alfa Hematinics Hematologic Agents Therapeutic Uses Pharmacologic Actions |
ClinicalTrials.gov processed this record on June 17, 2013