Beta Blockade in in Traumatic Brain Injury

• ClinicalTrials.gov Identifier: NCT02957331
• Recruitment Status: Completed
• First Posted: November 6, 2016
• Results First Posted: June 4, 2020
• Last Update Posted: June 4, 2020
• Sponsor: University of Tennessee
• Information provided by (Responsible Party): University of Tennessee

Study Description

Brief Summary:

The purpose of this study is test the effect of beta-adrenergic blockade on mortality in patients with traumatic brain injury with the hypothesis being that the addition of beta blockade to the treatment regime of this patient population will lower mortality and supress the catecholamine surge that accompanies traumatic brain injury as compared to those who do not receive beta blockade.

Half the patients will be randomized to receive propranolol and half will be randomized to receive no beta blocker.

Condition or disease	Intervention/treatment	Phase
Brain Injuries, Traumatic	Drug: Propranolol	Phase 4

Detailed Description:

The use of Beta-adrenergic blockade is not currently the standard of care of patients with traumatic brain injury. Traumatic brain injury is a common problem in our society with greater than 1.5 million cases occurring annually and over 50,000 deaths per year in the civilian population in the United States. Medical therapy has long consisted of monitoring intracranial pressure and supportive measures designed to limit intracranial pressure. Two retrospective observational studies completed at the University of Tennessee demonstrate that the addition of beta-adrenergic blockage to the treatment of the traumatic brain injury lessens mortality. The basis for conducting this study was established by retrospective data showing no harm to patients receiving Inderal and potential benefit. Available data, including data from the University of Tennessee, are retrospective and are limited to simple exposure to the drug. The proposed study will attempt to further quantify the effect by dosing with the drug to actual beta-blockade instead of simple exposure to the drug.

The effect of propranolol at the dosing levels used in this research will be determined by measurement of urinary catecholamines in both study arms and comparison of the actual effect of the drug on the catecholamine surge that occurs following traumatic brain injury will be determined.

Additionally, the effect of healthcare disparities on outcomes in patients with traumatic brain injury will be measured. Outcomes will be stratified by payer status and ethnicity to determine the effect each of these variables has on outcomes.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 26 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Beta-Adrenergic Blockade for Suppression of Catecholamine Surge Following Traumatic Brain Injury: A Randomized Trial
• Actual Study Start Date: January 2016
• Actual Primary Completion Date: May 2018
• Actual Study Completion Date: May 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: Propranolol arm; One half of qualifying and consenting subjects will be randomized to receive propranolol. This group will receive study drug 3 times daily (every 8 hours) starting at 20 mg. The dosage may be increased by up to 60 mg/day divided over three daily doses (or an additional 20 mg/dose) as necessary until the heart rate is less than 100. Study drug will be held for hypotension (systolic <100) or bradycardia (heart rate <60 beats per minute). The maximum daily dose for the treatment of hypertension of 640 mg will not be exceeded in this study.	Drug: Propranolol; Other Name: Inderal
No Intervention: Non propranolol arm; Non beta blockade arm will receive standard of care treatment and will not receive beta blockade. If a subject randomized to no Inderal develops hypertension and increased heart rate, he/she will be treated according to standard of care by the trauma team caring for the patient.

Outcome Measures

Primary Outcome Measures :

1. Mortality [ Time Frame: 30 day ]
   Mortality will be assessed at day 30 or at hospital discharge

Secondary Outcome Measures :

1. Urine Catecholamine Levels [ Time Frame: Collected at baseline, Day 2, Day 5, Day 10 and Day 14. ]
   Urine catecholamine levels will be measured in the hospital laboratory

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Subjects ages 18 and older with isolated traumatic brain injury as defined by Glasgow Coma Scale score 12 or less with documented injury on head CT and limited injury to the rest of the body. (Abbreviated Injury Scale (AIS) must be < or = 3 from other body areas.)

Exclusion Criteria:

• Subjects <18 years of age, prisoners, those on beta-blockers as home medication, those who are pregnant, those with severe liver disease, those taking vasopressors, those with acute coronary syndrome, and those with severe injury to another body region (AIS >3).
• Subjects who cannot be enrolled within 48 hours of admission following acute resuscitation will not be enrolled into this study.

Contacts and Locations

Locations

United States, Tennessee

Regional One Health

Memphis, Tennessee, United States, 38103

Sponsors and Collaborators

University of Tennessee

Investigators

• Principal Investigator: Thomas J. Schroeppel, MD; University of Tennessee Health Science Center

  Study Documents (Full-Text)

Documents provided by University of Tennessee:

Study Protocol and Statistical Analysis Plan  [PDF] September 19, 2019

More Information

Publications:

Kun LE, Gajjar A, Muhlbauer M, Heideman RL, Sanford R, Brenner M, Walter A, Langston J, Jenkins J, Facchini S. Stereotactic injection of herpes simplex thymidine kinase vector producer cells (PA317-G1Tk1SvNa.7) and intravenous ganciclovir for the treatment of progressive or recurrent primary supratentorial pediatric malignant brain tumors. Hum Gene Ther. 1995 Sep;6(9):1231-55.

Pople IK, Sanford RA, Muhlbauer MS. Clinical presentation and management of 100 infants with occipital plagiocephaly. Pediatr Neurosurg. 1996 Jul;25(1):1-6.

Gajjar A, Sanford RA, Bhargava R, Heideman R, Walter A, Li Y, Langston JW, Jenkins JJ, Muhlbauer M, Boyett J, Kun LE. Medulloblastoma with brain stem involvement: the impact of gross total resection on outcome. Pediatr Neurosurg. 1996 Oct;25(4):182-7.

Aggarwal R, Yeung D, Kumar P, Muhlbauer M, Kun LE. Efficacy and feasibility of stereotactic radiosurgery in the primary management of unfavorable pediatric ependymoma. Radiother Oncol. 1997 Jun;43(3):269-73.

Chuba PJ, Aronin P, Bhambhani K, Eichenhorn M, Zamarano L, Cianci P, Muhlbauer M, Porter AT, Fontanesi J. Hyperbaric oxygen therapy for radiation-induced brain injury in children. Cancer. 1997 Nov 15;80(10):2005-12.

Gajjar A, Sanford RA, Heideman R, Jenkins JJ, Walter A, Li Y, Langston JW, Muhlbauer M, Boyett JM, Kun LE. Low-grade astrocytoma: a decade of experience at St. Jude Children's Research Hospital. J Clin Oncol. 1997 Aug;15(8):2792-9.

Mühlbauer M, Pfisterer W, Eyb R, Knosp E. Minimally invasive retroperitoneal approach for lumbar corpectomy and anterior reconstruction. Technical note. J Neurosurg. 2000 Jul;93(1 Suppl):161-7.

Fletcher DT, Warner WC, Muhlbauer MS, Merchant TE. Cervical subluxation after surgery and irradiation of childhood ependymoma. Pediatr Neurosurg. 2002 Apr;36(4):189-96.

Williams RF, Magnotti LJ, Croce MA, Hargraves BB, Fischer PE, Schroeppel TJ, Zarzaur BL, Muhlbauer M, Timmons SD, Fabian TC. Impact of decompressive craniectomy on functional outcome after severe traumatic brain injury. J Trauma. 2009 Jun;66(6):1570-4; discussion 1574-6. doi: 10.1097/TA.0b013e3181a594c4.

DiCocco JM, Fabian TC, Emmett KP, Magnotti LJ, Zarzaur BL, Bate BG, Muhlbauer MS, Khan N, Kelly JM, Williams JS, Croce MA. Optimal outcomes for patients with blunt cerebrovascular injury (BCVI): tailoring treatment to the lesion. J Am Coll Surg. 2011 Apr;212(4):549-57; discussion 557-9. doi: 10.1016/j.jamcollsurg.2010.12.035.

Murphy RF, Cohen BH, Muhlbauer MS, Eubanks JW 3rd, Sawyer JR, Moisan A, Kelly DM. An accessory limb with lipomyelomeningocele in a male. Pediatr Surg Int. 2013 Jul;29(7):749-52. doi: 10.1007/s00383-013-3269-9. Epub 2013 Feb 8.

Klimo P Jr, Astur N, Gabrick K, Warner WC Jr, Muhlbauer MS. Occipitocervical fusion using a contoured rod and wire construct in children: a reappraisal of a vintage technique. J Neurosurg Pediatr. 2013 Feb;11(2):160-9. doi: 10.3171/2012.9.PEDS12214. Epub 2012 Nov 16.

Astur N, Klimo P Jr, Sawyer JR, Kelly DM, Muhlbauer MS, Warner WC Jr. Traumatic atlanto-occipital dislocation in children: evaluation, treatment, and outcomes. J Bone Joint Surg Am. 2013 Dec 18;95(24):e194(1-8). doi: 10.2106/JBJS.L.01295.

Astur N, Sawyer JR, Klimo P Jr, Kelly DM, Muhlbauer M, Warner WC Jr. Traumatic atlanto-occipital dislocation in children. J Am Acad Orthop Surg. 2014 May;22(5):274-82. doi: 10.5435/JAAOS-22-05-274. Review.

Befeler AR, Gordon W, Khan N, Fernandez J, Muhlbauer MS, Sorenson JM. Results of delayed follow-up imaging in traumatic brain injury. J Neurosurg. 2016 Mar;124(3):703-9. doi: 10.3171/2015.4.JNS141257. Epub 2015 Oct 16.

• Responsible Party: University of Tennessee
• ClinicalTrials.gov Identifier: NCT02957331
• Other Study ID Numbers: IRB # 15-04069-FB
• First Posted: November 6, 2016
• Results First Posted: June 4, 2020
• Last Update Posted: June 4, 2020
• Last Verified: October 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Additional relevant MeSH terms:

Brain Injuries; Brain Injuries, Traumatic; Wounds and Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Propranolol; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs; Anti-Arrhythmia Agents; Antihypertensive Agents; Vasodilator Agents