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

NCT00313716 | Completed Phase 2 Results DMC

• 1 other identifier: P01NS038660
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

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.

Conditions

Anemia; Traumatic Brain Injury

Keywords

anemia; traumatic brain injury; recombinant human erythropoietin; rhEpo; erythropoietin; TBI; Epo

Outcome Measures

Primary Outcomes (1)

• Glasgow Outcome Scale

  Dichotomized to favorable outcome (good recovery or moderate disability) or to unfavorable outcome (severe disability or vegetative or dead)

  at 6 months after injury

Secondary Outcomes (4)

• 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

Study Arms (6)

Epo1 and TT10

ACTIVE COMPARATOR

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

Epo1 and TT7

ACTIVE COMPARATOR

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

Epo2 and TT10

ACTIVE COMPARATOR

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

Epo2 and TT7

ACTIVE COMPARATOR

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

Placebo and TT10

PLACEBO COMPARATOR

Placebo administration and transfusion threshold 10 gm/dl

Other: placebo

Placebo and TT7

PLACEBO COMPARATOR

Placebo administration and transfusion threshold 7 gm/dl

Other: placebo

Interventions

recombinant human erythropoietin, rhEpo DRUG

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).

Epo1 and TT10; Epo1 and TT7; Epo2 and TT10; Epo2 and TT7

placebo OTHER

an inactive substance

Placebo and TT10; Placebo and TT7

Eligibility Criteria

• Age: 15 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Claudia Sue Robertson: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (1)

Baylor College of Medicine, Ben Taub General Hospital

Houston, Texas, 77030, United States

Location

Related Publications (5)

• 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.

  PMID: 25058216 RESULT

• 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.

  PMID: 27630085 DERIVED

• 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.

  PMID: 26496111 DERIVED

• 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.

  PMID: 26491799 DERIVED

• 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.

  PMID: 24686108 DERIVED

MeSH Terms

Conditions

Anemia; Brain Injuries, Traumatic

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases; Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Results Point of Contact

• Title: Claudia Robertson, MD
• Organization: Baylor College of Medicine

claudiar@bcm.edu

713-873-2792

Study Officials

• Claudia Robertson, MD

  Professor, Department of Neurosurgery, Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, Department of Neurosurgery

Study Record Dates

• First Submitted: April 10, 2006
• First Posted: April 12, 2006
• Study Start: April 1, 2006
• Primary Completion: March 1, 2013
• Study Completion: March 1, 2013
• Last Updated: September 10, 2014
• Results First Posted: September 10, 2014

Record last verified: 2014-09

Locations

US (1)