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

Phase 2

Completed

• Conditions: Anemia; Traumatic Brain Injury
• Interventions: Drug: recombinant human erythropoietin, rhEpo; Other: placebo

• Registration Number: NCT00313716
• Lead Sponsor: Claudia Sue Robertson

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.

Study Timeline

• Study Start: 2006-04
• Study First Submitted: 2006-04-10
• Study First Submitted QC: 2006-04-10
• Study First Posted: 2006-04-12
• Primary Completion: 2013-03
• Study Completion: 2013-03
• Results First Submitted: 2014-07-28
• Status Verified: 2014-09
• Results First Submitted QC: 2014-09-02
• Last Update Submitted: 2014-09-02
• Results First Posted: 2014-09-10
• Last Update Posted: 2014-09-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 200

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Epo1 and TT10	recombinant human erythropoietin, rhEpo	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
Epo1 and TT7	recombinant human erythropoietin, rhEpo	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
Epo2 and TT10	recombinant human erythropoietin, rhEpo	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
Epo2 and TT7	recombinant human erythropoietin, rhEpo	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
Placebo and TT10	placebo	Placebo administration and transfusion threshold 10 gm/dl
Placebo and TT7	placebo	Placebo administration and transfusion threshold 7 gm/dl

Primary Outcome Measures

Name	Time	Method
Glasgow Outcome Scale	at 6 months after injury	Dichotomized to favorable outcome (good recovery or moderate disability) or to unfavorable outcome (severe disability or vegetative or dead)

Secondary Outcome Measures

Name	Time	Method
Disability Rating Scale	at 6 months	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	up to 6 months after injury	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)	within 30 days after injury	development of ARDS was a primary safety outcome for the transfusion threshold randomization
Incidence of Infection	within 30 days after injury	occurrence of infection was a primary safety outcome for the transfusion threshold randomization

Trial Locations

Locations (1)

Baylor College of Medicine, Ben Taub General Hospital; 🇺🇸 Houston, Texas, United States