Clinical trial NCT00313716: Effects of Erythropoietin on Cerebral Vascular Dysfunction and Anemia in Traumatic Brain Injury
Official title: Effects of Erythropoietin on Cerebral Vascular Dysfunction and Anemia in Traumatic Brain Injury
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Anemia
Traumatic Brain Injury
Keywords: anemia
traumatic brain injury
recombinant human erythropoietin
rhEpo
erythropoietin
TBI
Epo
Lead sponsor: Baylor College of Medicine
Sponsor class: OTHER
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
First posted: 2006-04-12
Enrollment: 200
Sex: ALL
Minimum age (years): 15
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Glasgow Outcome Scale
timeFrame: at 6 months after injury
Secondary outcomes:
measure: Disability Rating Scale
timeFrame: at 6 months
measure: Mortality Rate
timeFrame: up to 6 months after injury
measure: Incidence of Adult Respiratory Distress Syndrome (ARDS)
timeFrame: within 30 days after injury
measure: Incidence of Infection
timeFrame: within 30 days after injury
Other outcomes:
Locations:
city: Houston
country: United States
facility: Baylor College of Medicine, Ben Taub General Hospital
state: Texas
Study officials:
affiliation: Professor, Department of Neurosurgery, Baylor College of Medicine
name: Claudia Robertson, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Aisiku 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.
citation: Yamal 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.
citation: Aisiku 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.
citation: Yamal 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.