Prehospital Tranexamic Acid Use for Traumatic Brain Injury

NCT01990768 | Completed Phase 2 Results DMC

• 3 other identifiers: 471145U01HL077863-09TATRC Log No. 13335004-A
• Study Type: interventional
• Target: 967
• Locations: 2 countries
• Sites: 12

Brief Summary

Primary aim: To determine the efficacy of two dosing regimens of TXA initiated in the prehospital setting in patients with moderate to severe TBI (GCS score ≤12). Primary hypothesis: The null hypothesis is that random assignment to prehospital administration of TXA in patients with moderate to severe TBI will not change the proportion of patients with a favorable long-term neurologic outcome compared to random assignment to placebo, based on the GOS-E at 6 months. Secondary aims: To determine differences between TXA and placebo in the following outcomes for patients with moderate to severe TBI treated in the prehospital setting with 2 dosing regimens of TXA:

• Clinical outcomes: ICH progression, Marshall and Rotterdam CT classification scores, DRS at discharge and 6 months, GOS-E at discharge, 28-day survival, frequency of neurosurgical interventions, and ventilator-free, ICU-free, and hospital-free days.
• Safety outcomes: Development of seizures, cerebral ischemic events, myocardial infarction, deep venous thrombosis, and pulmonary thromboembolism.
• Mechanistic outcomes: Alterations in fibrinolysis based on fibrinolytic pathway mediators and degree of clot lysis based on TEG. Inclusion: Blunt and penetrating traumatic mechanism consistent with TBI with prehospital GCS ≤ 12 prior to administration of sedative and/or paralytic agents, prehospital SBP ≥ 90 mmHg, prehospital intravenous (IV) access, age ≥ 15yrs (or weight ≥ 50kg if age is unknown), EMS transport destination based on standard local practices determined to be a participating trauma center. Exclusion: Prehospital GCS=3 with no reactive pupil, estimated time from injury to start of study drug bolus dose \>2 hours, unknown time of injury, clinical suspicion by EMS of seizure activity, acute MI or stroke or known history, to the extent possible, of seizures, thromboembolic disorders or renal dialysis, CPR by EMS prior to randomization, burns \> 20% TBSA, suspected or known prisoners, suspected or known pregnancy, prehospital TXA or other pro-coagulant drug given prior to randomization, subjects who have activated the "opt-out" process when required by the local regulatory board. A multi-center double-blind randomized controlled trial with 3 treatment arms:
• Bolus/maintenance: 1 gram IV TXA bolus in the prehospital setting followed by a 1 gram IV maintenance infusion initiated on hospital arrival and infused over 8 hours.
• Bolus only: 2 grams IV TXA bolus in the prehospital setting followed by a placebo maintenance infusion initiated on hospital arrival and infused over 8 hours.
• Placebo: Placebo IV bolus in the prehospital setting followed by a placebo maintenance infusion initiated on hospital arrival and infused over 8 hours.

Conditions

Traumatic Brain Injury

Keywords

tranexamic acid; traumatic brain injury; intracranial hemorrhage; prehospital; neurologic outcome; glasgow outcome scale extended; disability rating scale

Outcome Measures

Primary Outcomes (1)

• Dichotomized Glasgow Outcome Scale Extended (GOS-E) at 6 Months

  GOS-E subdivides the categories of severe and moderate disability and good recovery using a scale of 1 to 8 where 1 = death, 2 = vegetative state, 3 = lower severe disability, 4 = upper severe disability, 5 = lower moderate disability, 6 = upper moderate disability, 7 = lower good recovery, and 8 = upper good recovery. Structured telephone interviews have been developed and validated for the GOS-E and these questions were incorporated into the follow-up survey. GOS-E was dichotomized into unfavorable (1 to 4) and favorable (5 to 8) outcomes.

  6 months post-injury

Secondary Outcomes (17)

• Number of Participants Who Died Within 28 Days

  28 days after hospital arrival

• Disability Rating Scale (DRS) at 6 Months

  6 months post-injury

• Number of Participants With Unfavorable Outcome on Dichotomized Glasgow Outcome Scale Extended (GOS-E) at Discharge

  At the end of the hospital stay (average of 9 days post injury)

• Disability Rating Scale (DRS) at Discharge

  At the end of the hospital stay (average of 9 days post injury)

• Number of Participants With Intracranial Hemorrhage (ICH) Progression

  From hospital admission through 28 days or the end of the hospital stay if sooner (average of 13 days among patients with multiple scans)

Other Outcomes (1)

• Fibrinolysis at Hospital Admission

  First blood draw (average of 1.6 hours post-injury)

Study Arms (3)

1 gram Tranexamic Acid (TXA)

EXPERIMENTAL

Loading dose of 1 gram TXA given prior to hospital arrival followed by a 1 gram TXA infusion over 8 hours after hospital arrival

Drug: 1 gram Tranexamic Acid (TXA)

2 grams TXA

EXPERIMENTAL

Loading dose of 2 gram TXA given prior to hospital arrival followed by a placebo of 0.9% Sodium Chloride solution infusion over 8 hours after hospital arrival

Drug: 2 grams TXA

0.9% Sodium Chloride injectable

PLACEBO COMPARATOR

Loading dose of 0.9% Sodium Chloride solution given prior to hospital arrival followed by a placebo of 0.9% Sodium Chloride solution infusion over 8 hours after hospital arrival

Drug: 0.9% Sodium Chloride injectable

Interventions

1 gram Tranexamic Acid (TXA) DRUG

TXA produces an antifibrinolytic effect by competitively inhibiting the activation of plasminogen to plasmin.

Also known as: Cyklokapron

1 gram Tranexamic Acid (TXA)

2 grams TXA DRUG

TXA produces an antifibrinolytic effect by competitively inhibiting the activation of plasminogen to plasmin.

Also known as: Cyklokapron

2 grams TXA

0.9% Sodium Chloride injectable DRUG

Loading dose of 0.9% Sodium Chloride solution given prior to hospital arrival followed by a placebo of 0.9% Sodium Chloride solution infusion over 8 hours after hospital arrival. No active drug is added to the solution.

Also known as: Normal saline solution

0.9% Sodium Chloride injectable

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 or penetrating traumatic mechanism consistent with traumatic brain injury
• Prehospital Glasgow Coma Score (GCS) score ≤ 12 at any time prior to randomization and administration of sedative and/or paralytic agents
• Prehospital systolic blood pressure (SBP) ≥ 90 mmHg prior to randomization
• Prehospital intravenous (IV) or intraosseous (IO) access
• Estimated Age ≥ 15 (or estimated weight \> 50 kg if age is unknown)
• Emergency Medicine System (EMS) transport to a participating trauma center

You may not qualify if:

• Prehospital GCS=3 with no reactive pupil
• Estimated time from injury to hospital arrival \> 2 hours
• Unknown time of injury - no known reference times to support estimation
• Clinical suspicion by EMS of seizure activity or known history of seizures, acute myocardial infarction (MI) or stroke
• Cardio-pulmonary resuscitation (CPR) by EMS prior to randomization
• Burns \> 20% total body surface area (TBSA)
• Suspected or known prisoners
• Suspected or known pregnancy
• Prehospital TXA given prior to randomization
• Subjects who have activated the "opt-out" process when required by the local regulatory board

Sponsors & Collaborators

• University of Washington: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• U.S. Army Medical Research and Development Command: collaborator
• Canadian Institutes of Health Research (CIHR): collaborator
• Heart and Stroke Foundation of Canada: collaborator
• American Heart Association: collaborator
• Defence Research and Development Canada: collaborator

Study Sites (12)

Alabama Resuscitation Center

Birmingham, Alabama, 35249, United States

Location

Hennepin County Medical Center

Minneapolis, Minnesota, 55415, United States

Location

Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

Location

St Paul Regions Hospital

Saint Paul, Minnesota, 55101, United States

Location

University of Cincinnati Medical Center

Cincinnati, Ohio, 45267, United States

Location

Oregon Health & Sciences University

Portland, Oregon, 97239-3098, United States

Location

Dallas Center for Resuscitation Research

Dallas, Texas, 75390, United States

Location

Memorial Hermann Hospital - Texas Medical Center

Houston, Texas, 77030, United States

Location

Harborview Medical Center

Seattle, Washington, 98104, United States

Location

Milwaukee Resuscitation Research Center

Milwaukee, Wisconsin, 53226, United States

Location

British Columbia Regional Coordinating Center

Vancouver, British Columbia, V5Z 1 M9, Canada

Location

Toronto RescuNet

Toronto, Ontario, M5B 1W8, Canada

Location

Related Publications (4)

• Rowell S, Meier EN, Hoyos Gomez T, Fleming M, Jui J, Morrison L, Bulger E, Sopko G, Weisfeldt M, Christenson J, Klotz P, McMullan J, Callum J, Sheehan K, Tibbs B, Aufderheide T, Cotton B, Gandhi R, Idris A, Frascone RJ, Ferrara M, Richmond N, Kannas D, Schlamp R, Robinson B, Dries D, Tallon J, Hendrickson A, Gamber M, Garrett J, Simonson R, McKinley WI, Schreiber M. The effects of prehospital TXA on mortality and neurologic outcomes in patients with traumatic intracranial hemorrhage: A subgroup analysis from the prehospital TXA for TBI trial. J Trauma Acute Care Surg. 2024 Oct 1;97(4):572-580. doi: 10.1097/TA.0000000000004354. Epub 2024 Apr 30.

  PMID: 38685481 DERIVED

• Hoefer LE, Benjamin AJ, Polcari AM, Schreiber MA, Zakrison TL, Rowell SE. TXA does not affect levels of TBI-related biomarkers in blunt TBI with ICH: A secondary analysis of the prehospital TXA for TBI trial. J Trauma Acute Care Surg. 2024 Jan 1;96(1):94-100. doi: 10.1097/TA.0000000000004130. Epub 2023 Oct 9.

  PMID: 37807179 DERIVED

• Harmer JW, Dewey EN, Meier EN, Rowell SE, Schreiber MA. Tranexamic acid is not inferior to placebo with respect to adverse events in suspected traumatic brain injury patients not in shock with a normal head computed tomography scan: A retrospective study of a randomized trial. J Trauma Acute Care Surg. 2022 Jul 1;93(1):98-105. doi: 10.1097/TA.0000000000003635. Epub 2022 Mar 28.

  PMID: 35358154 DERIVED

• Rowell SE, Meier EN, McKnight B, Kannas D, May S, Sheehan K, Bulger EM, Idris AH, Christenson J, Morrison LJ, Frascone RJ, Bosarge PL, Colella MR, Johannigman J, Cotton BA, Callum J, McMullan J, Dries DJ, Tibbs B, Richmond NJ, Weisfeldt ML, Tallon JM, Garrett JS, Zielinski MD, Aufderheide TP, Gandhi RR, Schlamp R, Robinson BRH, Jui J, Klein L, Rizoli S, Gamber M, Fleming M, Hwang J, Vincent LE, Williams C, Hendrickson A, Simonson R, Klotz P, Sopko G, Witham W, Ferrara M, Schreiber MA. Effect of Out-of-Hospital Tranexamic Acid vs Placebo on 6-Month Functional Neurologic Outcomes in Patients With Moderate or Severe Traumatic Brain Injury. JAMA. 2020 Sep 8;324(10):961-974. doi: 10.1001/jama.2020.8958.

  PMID: 32897344 DERIVED

MeSH Terms

Conditions

Brain Injuries, Traumatic; Intracranial Hemorrhages

Interventions

Tranexamic Acid; Saline Solution

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Cerebrovascular Disorders; Vascular Diseases; Cardiovascular Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cyclohexanecarboxylic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Results Point of Contact

• Title: Dr. Susanne May
• Organization: University of Washington, Resuscitation Outcomes Consortium

rochelp@uwctc.org

206-685-1302

Study Officials

• Susanne May, PhD

  University of Washington

  PRINCIPAL INVESTIGATOR

• Martin Schreiber, MD FACS

  Oregon Health and Science University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: October 30, 2013
• First Posted: November 21, 2013
• Study Start: May 1, 2015
• Primary Completion: November 7, 2017
• Study Completion: November 7, 2017
• Last Updated: January 14, 2019
• Results First Posted: January 14, 2019

Record last verified: 2018-12

Data Sharing

• IPD Sharing: Will share

Locations

US (10); CA (2)