Brain Injuries, TraumaticPhase 4NCT02957331

Beta Blockade in in Traumatic Brain Injury

A Phase 4 study testing Propranolol in people with Brain Injuries, Traumatic, run by University of Tennessee at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial 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… Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Brain Injuries, Traumatic
What is being tested?: Propranolol
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 26 participants
Where: 1 siteUnited States
Study dates: Jan 2016to May 2018
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.)

Who cannot join

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.

Trial locations and contacts

1 site in 1 country.

United States1 site

Regional One Health
Memphis, Tennessee, 38103

Other trials in United States

About this study

Official title: Beta-Adrenergic Blockade for Suppression of Catecholamine Surge Following Traumatic Brain Injury: A Randomized Trial

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

Read the 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.

Conditions: Brain Injuries, Traumatic
Being tested: Propranolol
Medical subject headings: Brain Injuries, Traumatic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PropranololDrug
Also called Inderal

Study groups in NCT02957331
Study group	Role	What they receive
Propranolol arm	Experimental	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. Receives: Drug: Propranolol
Non propranolol arm	No intervention	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.

What is being measured

The primary outcome is the main question the study is designed to answer.

Mortality
Mortality will be assessed at day 30 or at hospital discharge
Measured: 30 day

Secondary outcomes (1)

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jan 2016May 2018

First posted7 Nov 2016 (estimated)
Study startJan 2016
Primary completionMay 2018
Study completionMay 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (15)Papers the sponsor has linked to this study.
Other trials for Brain Injuries, TraumaticStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 26 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02957331
Sponsor's protocol ID: IRB # 15-04069-FB
Status last verified: Oct 2018
First submitted: 31 Oct 2016
Last updated: 4 Jun 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: No

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. doi: 10.1089/hum.1995.6.9-1231.
PubMed 8527482
Pople IK, Sanford RA, Muhlbauer MS. Clinical presentation and management of 100 infants with occipital plagiocephaly. Pediatr Neurosurg. 1996 Jul;25(1):1-6. doi: 10.1159/000121088.
PubMed 9055327
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. doi: 10.1159/000121121.
PubMed 9293545
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. doi: 10.1016/s0167-8140(97)01926-9.
PubMed 9215786
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. doi: 10.1002/(sici)1097-0142(19971115)80:103.0.co;2-0.
PubMed 9366305
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. doi: 10.1200/JCO.1997.15.8.2792.
PubMed 9256121
Muhlbauer 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. doi: 10.3171/spi.2000.93.1.0161.
PubMed 10879777
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. doi: 10.1159/000056056.
PubMed 12006754
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.
PubMed 19509616
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.
PubMed 21463787
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.
PubMed 23392915
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.
PubMed 23157394
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.
PubMed 24352780
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.
PubMed 24788443
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.
PubMed 26473787

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Brain Injuries, Traumatic trials

Study at a glance

From the registry record, last updated by the sponsor on 4 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Beta-Adrenergic Blockade for Suppression of Catecholamine Surge Following Traumatic Brain Injury: A Randomized Trial
ClinicalTrials.gov ID: NCT02957331
Acronym / sponsor ID: IRB # 15-04069-FB
Conditions: Brain Injuries, Traumatic
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 26 participants (actual)
Lead sponsor: University of TennesseeUniversity, hospital or other
Study start: Jan 2016 (actual)
Primary completion: May 2018 (actual)
Study completion: May 2018 (actual)
First posted: 7 Nov 2016 (estimated)
Results: Posted 4 Jun 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Propranolol arm	Experimental	Drug: PropranololOne 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.
Non propranolol arm	No intervention	–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.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (1 listed)

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.)

Key exclusion criteria (2 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
PropranololAlso: Inderal	Drug	Propranolol arm

Primary outcome

Mortality
Time frame: 30 day
Mortality will be assessed at day 30 or at hospital discharge

1 secondary outcome

Urine Catecholamine Levels
Time frame: Collected at baseline, Day 2, Day 5, Day 10 and Day 14.

Results and safety

Results posted to the registry on 4 Jun 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Propranolol Arm	14	13
Non Propranolol Arm	12	12

Primary outcome: Mortality

Time frame: 30 day. Number. Unit: percentage of participants

Measure	Propranolol Arm n = 13	Non Propranolol Arm n = 12
Value	7.7	33.3

1 secondary outcome is reported in the full results.

Adverse events

Time frame: 24 months. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Propranolol Arm	0 of 13 (0%)	1 of 13 (7.7%)	1 of 13
Non Propranolol Arm	0 of 12 (0%)	0 of 12 (0%)	4 of 12

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 4 Jun 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 8527482Kun 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. doi: 10.1089/hum.1995.6.9-1231.
Background: PubMed 9055327Pople IK, Sanford RA, Muhlbauer MS. Clinical presentation and management of 100 infants with occipital plagiocephaly. Pediatr Neurosurg. 1996 Jul;25(1):1-6. doi: 10.1159/000121088.
Background: PubMed 9293545Gajjar 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. doi: 10.1159/000121121.
Background: PubMed 9215786Aggarwal 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. doi: 10.1016/s0167-8140(97)01926-9.
Background: PubMed 9366305Chuba 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. doi: 10.1002/(sici)1097-0142(19971115)80:103.0.co;2-0.
Background: PubMed 9256121Gajjar 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. doi: 10.1200/JCO.1997.15.8.2792.
Background: PubMed 10879777Muhlbauer 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. doi: 10.3171/spi.2000.93.1.0161.
Background: PubMed 12006754Fletcher DT, Warner WC, Muhlbauer MS, Merchant TE. Cervical subluxation after surgery and irradiation of childhood ependymoma. Pediatr Neurosurg. 2002 Apr;36(4):189-96. doi: 10.1159/000056056.
Background: PubMed 19509616Williams 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.
Background: PubMed 21463787DiCocco 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.
Background: PubMed 23392915Murphy 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.
Background: PubMed 23157394Klimo 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.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Thomas J. Schroeppel, MD principal investigator

University of Tennessee

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Propranolol in people with Brain Injuries, Traumatic, run by University of Tennessee at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 4 Jun 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mortality (time frame: 30 day). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02957331, which also lists 15 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jun 2020; AzTrials last refreshed its copy on 30 Oct 2026.