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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Claudia Sue Robertson, Baylor College of Medicine
ClinicalTrials.gov Identifier:
NCT00313716
First received: April 10, 2006
Last updated: September 2, 2014
Last verified: September 2014
  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

Resource links provided by NLM:


Further study details as provided by Baylor College of Medicine:

Primary Outcome Measures:
  • Glasgow Outcome Scale [ Time Frame: at 6 months after injury ] [ Designated as safety issue: No ]
    Dichotomized to favorable outcome (good recovery or moderate disability) or to unfavorable outcome (severe disability or vegetative or dead)


Secondary Outcome Measures:
  • Disability Rating Scale [ Time Frame: at 6 months ] [ Designated as safety issue: No ]
    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.

  • Mortality Rate [ Time Frame: up to 6 months after injury ] [ Designated as safety issue: Yes ]
    mortality rate was a secondary outcome measure for the Epo randomization, and a primary safety outcome measure for the transfusion threshold randomization

  • Incidence of Adult Respiratory Distress Syndrome (ARDS) [ Time Frame: within 30 days after injury ] [ Designated as safety issue: Yes ]
    development of ARDS was a primary safety outcome for the transfusion threshold randomization

  • Incidence of Infection [ Time Frame: within 30 days after injury ] [ Designated as safety issue: Yes ]
    occurrence of infection was a primary safety outcome for the transfusion threshold randomization


Enrollment: 200
Study Start Date: April 2006
Study Completion Date: March 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Epo1 and TT10
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
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. 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).
Active Comparator: Epo1 and TT7
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
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. 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).
Active Comparator: Epo2 and TT10
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
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. 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).
Active Comparator: Epo2 and TT7
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
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. 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).
Placebo Comparator: Placebo and TT10
Placebo administration and transfusion threshold 10 gm/dl
Other: placebo
an inactive substance
Placebo Comparator: Placebo and TT7
Placebo administration and transfusion threshold 7 gm/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
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00313716

Locations
United States, Texas
Baylor College of Medicine, Ben Taub General Hospital
Houston, Texas, United States, 77030
Sponsors and Collaborators
Claudia Sue Robertson
Investigators
Principal Investigator: Claudia Robertson, MD Professor, Department of Neurosurgery, Baylor College of Medicine
  More Information

No publications provided by Baylor College of Medicine

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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
Results First Received: July 28, 2014
Last Updated: September 2, 2014
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
Brain Diseases
Central Nervous System Diseases
Craniocerebral Trauma
Hematologic Diseases
Nervous System Diseases
Trauma, Nervous System
Wounds and Injuries
Epoetin alfa
Hematinics
Hematologic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014