Beta Blocker Use In Traumatic Brain Injury Based On The High-Sensitive Troponin T Status

NCT04508244 | Unknown Phase 4 DMC

• 1 other identifier: IRGC-05-SI-18-293
• Study Type: interventional
• Target: 771
• Locations: 1 country
• Sites: 1

Brief Summary

Beta blockers (BB) play an important role in protection of end organs that are susceptible for secondary injury by the Traumatic brain injury (TBI)-induced catecholamine surge. However, use of BBs in trauma patients is not yet the standard of care which necessitates clear scientific evidence and justification to be used especially in TBI patients. The BBTBBT study aims to determine whether early administration of propranolol based on the HSTnT status will improve the outcome of mild-to-severe TBI patients. Our primary hypothesis is that BBs are effective in reducing 10 and 30-day mortality in TBI patients.BBs are effective in reducing 10 and 30-day mortality in TBI patients. Methods/Design: The BBTBBT study is a prospective, randomized, double-blinded, placebo-controlled trial, three-arm trial of BB use in mild-to-severe TBI patients based on the HsTnT status.

Conditions

Trauma; Brain Injuries; Stress Reaction; Beta Blockers; Troponin

Keywords

propranolol; troponin; biomarkers; myocardial injury; brain injury; trauma; qatar

Outcome Measures

Primary Outcomes (2)

• Mortality

  Number of participants who died from each study arm

  10 days

• Mortality

  Number of participants who died from each study arm

  30 days

Secondary Outcomes (2)

• Duration of hospital stay

  3 months

• Functional status

  3 months

Other Outcomes (1)

• Injury severity indicators

  48 hours

Study Arms (3)

TBI with positive troponin

ACTIVE COMPARATOR

Patients will receive IV propranolol for 6 days

Drug: Propranolol

TBI with negative troponin (a)

PLACEBO COMPARATOR

Patients will receive IV placebol for 6 days

Drug: Placebo

TBI with negative troponin (b)

EXPERIMENTAL

Patients will receive IV propranolol for 6 days

Drug: Propranolol

Interventions

Placebo DRUG

12 ampoules of 1 mg placebo solution (3 ampoules/day for 2 days; 2 ampoules/day for day-3 \& 4 and 1 ampoule/day for day-5 \& 6.

TBI with negative troponin (a)

Propranolol DRUG

12 ampoules of 1 mg placebo solution (3 ampoules/day for 2 days; 2 ampoules/day for day-3 \& 4 and 1 ampoule/day for day-5 \& 6.

Also known as: inderal

TBI with negative troponin (b); TBI with positive troponin

Eligibility Criteria

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

You may qualify if:

• All adults (≥18 -65 years)
• both genders
• mild-to-severe blunt TBI (head AIS 1-5 and/ GCS 4-15) patients requiring hospital admission

You may not qualify if:

• Patients \<18 and\> 65 yrs old
• penetrating trauma
• non-survivable injuries (head AIS=6 \& GCS=3)
• uncontrolled bleeding on arrival to ED
• pregnant women
• prisoners
• patients with heart rate (HR) ≤70, systolic blood pressure (SBP) ≤100 mmHg (or MAP \<70 mmHg) not responding to initial management or required to be maintained on vasopressors on arrival .
• Patients who will undergo hypothermia therapy,
• any penetrating injury to head, thorax or abdomen,
• history of bronchial asthma
• patients posted for emergency surgery during the first 6 hrs.

Sponsors & Collaborators

• Hamad Medical Corporation: lead

Study Sites (1)

Hamad General Hospital

Doha, Qatar

RECRUITING

Related Publications (18)

• Faul M, Xu L, Wald MM, Coronado VG. Traumatic Brain Injury in the United States: Emergency Department Visits, Hospitalizations, and Deaths. Atlanta, GA: Centers for Disease Control and Prevention, National Center for Injury Prevention and Control; 2010.

  BACKGROUND

• Ma VY, Chan L, Carruthers KJ. Incidence, prevalence, costs, and impact on disability of common conditions requiring rehabilitation in the United States: stroke, spinal cord injury, traumatic brain injury, multiple sclerosis, osteoarthritis, rheumatoid arthritis, limb loss, and back pain. Arch Phys Med Rehabil. 2014 May;95(5):986-995.e1. doi: 10.1016/j.apmr.2013.10.032. Epub 2014 Jan 21.

  PMID: 24462839 BACKGROUND

• Mock C, Lormand JD, Goosen J, Joshipura M, Peden M. Guidelines for essential trauma care. Geneva, World Health Organization, 2004. Retrieved from: http://www.who.int/violence_injury_prevention/publications/services/en/guidelines_traumacare.pdf

  BACKGROUND

• Al-Otaiby MA, Al-Amri HS, Al-Moghairi AM. The clinical significance of cardiac troponins in medical practice. J Saudi Heart Assoc. 2011 Jan;23(1):3-11. doi: 10.1016/j.jsha.2010.10.001. Epub 2010 Oct 20.

  PMID: 23960628 BACKGROUND

• Mahmood I, El-Menyar A, Dabdoob W, Abdulrahman Y, Siddiqui T, Atique S, Arumugam SK, Latifi R, Al-Thani H. Troponin T in Patients with Traumatic Chest Injuries with and without Cardiac Involvement: Insights from an Observational Study. N Am J Med Sci. 2016 Jan;8(1):17-24. doi: 10.4103/1947-2714.175188.

  PMID: 27011943 BACKGROUND

• Edouard AR, Felten ML, Hebert JL, Cosson C, Martin L, Benhamou D. Incidence and significance of cardiac troponin I release in severe trauma patients. Anesthesiology. 2004 Dec;101(6):1262-8. doi: 10.1097/00000542-200412000-00004.

  PMID: 15564931 BACKGROUND

• Hasanin A, Kamal A, Amin S, Zakaria D, El Sayed R, Mahmoud K, Mukhtar A. Incidence and outcome of cardiac injury in patients with severe head trauma. Scand J Trauma Resusc Emerg Med. 2016 Apr 27;24:58. doi: 10.1186/s13049-016-0246-z.

  PMID: 27121183 BACKGROUND

• Smith A, John M, Trout R, Davis E, Moningi S. Elevated cardiac troponins in sepsis: what do they signify? W V Med J. 2009 Jul-Aug;105(4):29-32.

  PMID: 19585902 BACKGROUND

• Lim W, Cook DJ, Griffith LE, Crowther MA, Devereaux PJ. Elevated cardiac troponin levels in critically ill patients: prevalence, incidence, and outcomes. Am J Crit Care. 2006 May;15(3):280-8; quiz 289.

  PMID: 16632770 BACKGROUND

• Poe S, Vandivier-Pletsch RH, Clay M, Wong HR, Haynes E, Rothenberg FG. Cardiac Troponin Measurement in the Critically Ill: Potential for Guiding Clinical Management. J Investig Med. 2015 Dec;63(8):905-15. doi: 10.1097/JIM.0000000000000239.

  PMID: 26425879 BACKGROUND

• Salim A, Hadjizacharia P, Brown C, Inaba K, Teixeira PG, Chan L, Rhee P, Demetriades D. Significance of troponin elevation after severe traumatic brain injury. J Trauma. 2008 Jan;64(1):46-52. doi: 10.1097/TA.0b013e31815eb15a.

  PMID: 18188098 BACKGROUND

• Bukur M, Mohseni S, Ley E, Salim A, Margulies D, Talving P, Demetriades D, Inaba K. Efficacy of beta-blockade after isolated blunt head injury: does race matter? J Trauma Acute Care Surg. 2012 Apr;72(4):1013-8. doi: 10.1097/TA.0b013e318241bc5b.

  PMID: 22491619 BACKGROUND

• Schroeppel TJ, Fischer PE, Zarzaur BL, Magnotti LJ, Clement LP, Fabian TC, Croce MA. Beta-adrenergic blockade and traumatic brain injury: protective? J Trauma. 2010 Oct;69(4):776-82. doi: 10.1097/TA.0b013e3181e981b8.

  PMID: 20938265 BACKGROUND

• Ko A, Harada MY, Barmparas G, Thomsen GM, Alban RF, Bloom MB, Chung R, Melo N, Margulies DR, Ley EJ. Early propranolol after traumatic brain injury is associated with lower mortality. J Trauma Acute Care Surg. 2016 Apr;80(4):637-42. doi: 10.1097/TA.0000000000000959.

  PMID: 26808028 BACKGROUND

• El-Menyar A, Asim M, Latifi R, Bangdiwala SI, Al-Thani H. Predictive value of positive high-sensitivity troponin T in intubated traumatic brain injury patients. J Neurosurg. 2018 Dec 1;129(6):1541-1549. doi: 10.3171/2017.7.JNS17675. Epub 2018 Jan 5.

  PMID: 29303440 BACKGROUND

• El-Menyar A, Goyal A, Latifi R, Al-Thani H, Frishman W. Brain-Heart Interactions in Traumatic Brain Injury. Cardiol Rev. 2017 Nov/Dec;25(6):279-288. doi: 10.1097/CRD.0000000000000167.

  PMID: 28984668 BACKGROUND

• El-Menyar A, Asim M, Khan N, Rizoli S, Mahmood I, Al-Ani M, Kanbar A, Alaieb A, Hakim S, Younis B, Taha I, Jogol H, Siddiqui T, Hammo AA, Abdurraheim N, Alabdallat M, Bahey AA, Ahmed K, Atique S, Chaudry IH, Prabhu KS, Uddin S, Al-Thani H. Systemic and cerebro-cardiac biomarkers following traumatic brain injury: an interim analysis of randomized controlled clinical trial of early administration of beta blockers. Sci Rep. 2024 Aug 23;14(1):19574. doi: 10.1038/s41598-024-70470-y.

  PMID: 39179700 DERIVED

• El-Menyar A, Asim M, Bahey AA, Chughtai T, Alyafai A, Abdelrahman H, Rizoli S, Peralta R, Al-Thani H. Beta blocker use in traumatic brain injury based on the high-sensitive troponin status (BBTBBT): methodology and protocol implementation of a double-blind randomized controlled clinical trial. Trials. 2021 Dec 7;22(1):890. doi: 10.1186/s13063-021-05872-8.

  PMID: 34876207 DERIVED

MeSH Terms

Conditions

Wounds and Injuries; Brain Injuries; Fractures, Stress

Interventions

Propranolol

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Fractures, Bone

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds

Study Officials

• Ayman El-Menyar, MD

  Hamad Medical Corporation

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ayman El-Menyar, MD

CONTACT

44396130; aelmenyar@hamad.qa

Mohammad Asim, PhD

CONTACT

masim1@hamad.qa

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Prospective, randomized, double-blinded, placebo-controlled trial

Study Record Dates

• First Submitted: July 24, 2020
• First Posted: August 11, 2020
• Study Start: December 29, 2020
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2024
• Last Updated: September 28, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

QA (1)