Effects of Erythropoietin on Cerebral Vascular Dysfunction and Anemia in Traumatic Brain Injury

Effects of Erythropoietin on Cerebral Vascular Dysfunction and Anemia in Traumatic Brain Injury

Sponsors

Lead Sponsor: Claudia Sue Robertson

Collaborator: National Institute of Neurological Disorders and Stroke (NINDS)

Source Baylor College of Medicine
Brief 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.

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.

Overall Status Completed
Start Date April 2006
Completion Date March 2013
Primary Completion Date March 2013
Phase Phase 2/Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
Glasgow Outcome Scale at 6 months after injury
Secondary Outcome
Measure Time Frame
Disability Rating Scale at 6 months
Mortality Rate up to 6 months after injury
Incidence of Adult Respiratory Distress Syndrome (ARDS) within 30 days after injury
Incidence of Infection within 30 days after injury
Enrollment 200
Condition
Intervention

Intervention Type: Drug

Intervention Name: recombinant human erythropoietin, rhEpo

Description: 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).

Intervention Type: Other

Intervention Name: placebo

Description: an inactive substance

Eligibility

Criteria:

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

Gender: All

Minimum Age: 15 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Claudia Robertson, MD Principal Investigator Professor, Department of Neurosurgery, Baylor College of Medicine
Location
Facility: Baylor College of Medicine, Ben Taub General Hospital
Location Countries

United States

Verification Date

September 2014

Responsible Party

Type: Sponsor-Investigator

Investigator Affiliation: Baylor College of Medicine

Investigator Full Name: Claudia Sue Robertson

Investigator Title: Professor, Department of Neurosurgery

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 6
Arm Group

Label: Epo1 and TT10

Type: Active Comparator

Description: 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

Label: Epo1 and TT7

Type: Active Comparator

Description: 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

Label: Epo2 and TT10

Type: Active Comparator

Description: 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

Label: Epo2 and TT7

Type: Active Comparator

Description: 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

Label: Placebo and TT10

Type: Placebo Comparator

Description: Placebo administration and transfusion threshold 10 gm/dl

Label: Placebo and TT7

Type: Placebo Comparator

Description: Placebo administration and transfusion threshold 7 gm/dl

Study Design Info

Allocation: Randomized

Intervention Model: Factorial Assignment

Primary Purpose: Treatment

Masking: Triple (Participant, Investigator, Outcomes Assessor)

Source: ClinicalTrials.gov