The Use of Tranexamic Acid in the Treatment of Symptomatic Subdural Hematoma (TRACE)

April 10, 2024 updated by: Unity Health Toronto

TRACE STUDY: A Randomized Controlled Trial Using Tranexamic Acid in the Treatment of Subdural Hematoma

Subdural hematoma (SDH) is a common condition experienced after head injury. Blood collects on the surface of the brain, causing headaches which can progress to confusion, weakness, or even coma. While patients with SDH often receive surgery, not all patients require surgery right away to ease pressure on the brain. After surgery, there can be up to 30 percent chance of more bleeding and the need for more surgeries. Given this, a drug capable of lowering the chance of more bleeding and speeding the recovery of the patient is highly desirable. In this study, we will test a commonly used, cheap drug called Tranexamic Acid (TXA). While the body stops unwanted and sometimes dangerous bleeding naturally by forming blood clots, TXA stops these blood clots from breaking down, which helps to keep bleeding spots plugged. Our previous study showed that TXA helped speed up patients' recovery; but a larger number of patients is necessary to evaluate how well TXA works to reduce bleeding and improve patient-reported outcomes. In this study, regardless of the need for surgery, half of the patients will be randomly assigned to take TXA, while the other half will take a placebo, which is a look-alike substance that contains no active drug. We will measure multiple outcomes over time to determine if TXA is working and lowers healthcare and personal costs, while also taking blood and surgical samples, to better understand how this drug works in SDH patients.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

130

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5B1T8
        • St. Michael's Hospital
        • Contact:
        • Principal Investigator:
          • Michael D Cusimano, MD, PhD
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

45 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients aged 45 and older weighing between 45-150 kg diagnosed with symptomatic SDH will be included. SDH is defined as unilateral or bilateral crescentic collection of blood (hyper, iso, or hypodense, or mixed density) of greater than or equals to 8 mm in thickness along the cerebral convexity on CT of the head. Symptomatic SDH patients eligible for inclusion are those with SDH with one or more of the following symptoms attributable to the SDH: headache, gait disturbance, confusion or cognitive decline, limb weakness or numbness/paresthesia, speech or visual disturbance, drowsiness or impaired consciousness, seizures, impaired cognition, or memory loss at the time of assessment.

Exclusion Criteria:

- Patients will be excluded for any of the following conditions:

  1. Asymptomatic for longer than 72 hours
  2. SDH less than 8 mm in maximal thickness
  3. Have an acutely deteriorating neurological status (e.g., brain herniation with pupillary dilation, aneurysm rupture, etc.) that is likely to be fatal within 6 hours or less due to a predominantly acute SDH
  4. Presence of brain contusion larger than 5 cubic centimeters or subarachnoid hemorrhage (SAH) thicker than 10 mm with Glasgow Coma Scale (GCS)< 13
  5. Patients with primarily interhemispheric or tentorial SDH
  6. Hypersensitivity to TXA or any of the placebo ingredients
  7. Pregnancy
  8. Irregular menstrual bleeding with unidentified cause
  9. Known acquired colour vision disturbances
  10. Hematuria caused by renal parenchymal disease
  11. Acute and chronic renal insufficiency indicated by estimated Glomerular Filtration Rate (eGFR) ≤ 30 mL/min
  12. Concomitant intake of birth control pill and/or hormonal replacement therapy, and anti-inhibitor coagulant concentrates (factor VIII inhibitor bypass activity (FEIBA), factor VII, activated factor IX)
  13. Consumption coagulopathy/disseminated intravascular coagulation (DIC) in the last 7 days
  14. Not competent to take study medication properly and regularly or not having access to caregiver that is able to comply with study medication administration
  15. Mechanical heart valve
  16. Contraindication to stopping full therapeutic doses of non-acetylsalicylic acid antiplatelets, warfarin, direct oral anticoagulant (e.g., apixaban) or other anticoagulant for 2 weeks after surgery or recent blood clot and/or recent thromboembolic complications in the last 2 weeks
  17. SDH caused by intracranial hypotension
  18. Known thrombophilia (e.g., antiphospholipid syndrome)
  19. Any active malignancy: metastatic cancer systemically or to the brain or a primary malignant brain tumour treated within the last 6 months
  20. Previous enrolment in this trial for a prior episode
  21. Time interval >3 days from the time of clinical assessment to eligibility assessment
  22. Patients weighing <45 kg or >150 kg

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Standard care + TXA
Non-surgical patients will be given a single oral or IV loading dose of TXA within three hours of being randomized. For surgical patients, the same loading dose will be administered whenever possible prior to surgery. Patients who are able to swallow will be given an oral loading dose of 1g TXA. Patients who are unable to swallow will be given an IV loading dose of 1g TXA which will be added to a 100mL infusion bag of NaCl 0.9% and infused by slow intravenous injection over 20 minutes. After 12 hours of the loading dose, patients will be given 500 mg TXA by mouth (or IV for those unable to swallow) three times a day, totalling 1500 mg/day, for 45 days.
Drug: Tranexamic acid (TXA)
GD-Tranexamic Acid 500 mg oral tablet over-encapsulated to match the placebo. Sandoz-Tranexamic Acid 100 mg/mL solution for injection via intravenous (IV) added to a 100mL infusion bag of NaCl 0.9% and infused by slow intravenous injection over 20 minutes.
Other Names:
  • Cyklokapron
Placebo Comparator: Standard care + placebo
Non-surgical patients will be given a single oral or IV loading dose of placebo within three hours of being randomized. For surgical patients, the same loading dose will be administered whenever possible prior to surgery. Patients who are able to swallow will be given an oral loading dose of 1g placebo (gelatin capsule composed of microcrystalline cellulose 105 powder NF). Patients who are unable to swallow will be given an IV loading dose of 1g placebo (sodium chloride also known as NaCl 0.9%). After 12 hours of the loading dose, patients will be given 500 mg placebo by mouth (or IV for those unable to swallow) three times a day, totalling 1500 mg/day, for 45 days.
Drug: Placebo
Placebo 500 mg consisting of an identical capsule to over-encapsulated tranexamic acid oral tablet entirely filled with microcrystalline cellulose, and sealed. Placebo 100 mg/mL solution for injection via intravenous (IV) consisting of 0.9% sodium chloride (saline).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
European Quality of Life 5 Dimensions 5 Level Version (EQ-5D-5L)
Time Frame: Every 2 weeks after randomization up to 45±10 days.
A self-rated questionnaire that assesses a patient's health state in five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.
Every 2 weeks after randomization up to 45±10 days.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Patient-Reported Outcomes Measurement Information System (PROMIS) Scale v1.2 - Global Health. English and French versions
Time Frame: Baseline and every 2 weeks after randomization up to 45±10 days, and then at 60-90 days, and 180±10 days after randomization.
A 10-item measure that assesses an individual's general physical, mental, and social health as it is intended to globally reflect individuals' assessment of their physical and mental health in the last 7 days.
Baseline and every 2 weeks after randomization up to 45±10 days, and then at 60-90 days, and 180±10 days after randomization.
PROMIS Item Bank v2.0 - Cognitive Function. English version
Time Frame: Baseline and every 2 weeks after randomization up to 45±10 days, and then at 60-90 days, and 180±10 days after randomization.
A measure that assesses cognitive function that will be administered as a computer adaptive test.
Baseline and every 2 weeks after randomization up to 45±10 days, and then at 60-90 days, and 180±10 days after randomization.
PROMIS Item Bank v2.0 - Physical Function. English version
Time Frame: Baseline and every 2 weeks after randomization up to 45±10 days, and then at 60-90 days, and 180±10 days after randomization.
A measure that assesses self-reported capability rather than actual performance of physical activities that will be administered as a computer adaptive test.
Baseline and every 2 weeks after randomization up to 45±10 days, and then at 60-90 days, and 180±10 days after randomization.
PROMIS Item Bank v2.0 - Ability to Participate in Social Roles and Activities. English version
Time Frame: Baseline and every 2 weeks after randomization up to 45±10 days, and then at 60-90 days, and 180±10 days after randomization.
A measure that assesses the perceived ability to perform one's usual social roles and activities that will be administered as a computer adaptive test. The item bank does not use a time frame (e.g. over the past 7 days) when assessing ability to participate in social roles and activities.
Baseline and every 2 weeks after randomization up to 45±10 days, and then at 60-90 days, and 180±10 days after randomization.
Subdural hematoma volume change
Time Frame: Baseline, 45±10 days after randomization, and 60-90 days if deemed necessary for the patient's routine care.
Change in hematoma volume in millilitres on CT scan.
Baseline, 45±10 days after randomization, and 60-90 days if deemed necessary for the patient's routine care.
Number of subdural hematoma-related surgical interventions
Time Frame: First admission, subsequent admissions up to 180 days after randomization
First admission, subsequent admissions up to 180 days after randomization
Recurrence rate of SDH
Time Frame: 45±10 days, 60-90 days, and 180±10 days after randomization
45±10 days, 60-90 days, and 180±10 days after randomization
Mortality
Time Frame: During the course of study up to 180±10 days after randomization
During the course of study up to 180±10 days after randomization
Modified Rankin Scale
Time Frame: Baseline, 45±10 days, 60-90 days, and 180±10 days after randomization
A 6-point disability scale used to measure the degree of disability in patients who have had a stroke.
Baseline, 45±10 days, 60-90 days, and 180±10 days after randomization
Disability Rating Scale
Time Frame: Baseline, 45±10 days, 60-90 days, and 180±10 days after randomization
Eight questions regarding body function, activity, participation, communication, and movements each rated on a 3-5-point scale that is summed to give a total score.
Baseline, 45±10 days, 60-90 days, and 180±10 days after randomization
Medical Consumption Questionnaire
Time Frame: Baseline, 45±10 days, and 180±10 days after randomization
Health-related cost questionnaire on the use of healthcare in the past month.
Baseline, 45±10 days, and 180±10 days after randomization
EQ-5D-5L
Time Frame: Baseline, 60-90 days, and 180±10 days after randomization
A self-rated questionnaire that assesses a patient's health state in five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.
Baseline, 60-90 days, and 180±10 days after randomization
Adverse events
Time Frame: Discharge, 45±10 days, 60-90 days, and 180±10 days after randomization
Adverse events of grade 3 or higher as defined by Good Clinical Practice Guidelines.
Discharge, 45±10 days, 60-90 days, and 180±10 days after randomization
Length of stay in hospital due to subdural hematoma
Time Frame: During the course of the study up to 180±10 days after randomization
During the course of the study up to 180±10 days after randomization
Disposition after discharged from hospital
Time Frame: During the course of the study up to 180±10 days after randomization
During the course of the study up to 180±10 days after randomization
Montreal Cognitive Assessment
Time Frame: Baseline, 45±10 days, and 60-90 days after randomization
This assessment evaluates the patient's cognition based on eight areas: visuospatial/executive function, naming, memory, attention, language, abstraction, delayed recall, and orientation.
Baseline, 45±10 days, and 60-90 days after randomization

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Unity Health Toronto

Collaborators

Canadian Institutes of Health Research (CIHR)
The Physicians' Services Incorporated Foundation
Applied Health Research Centre

Investigators

  • Principal Investigator: Michael D Cusimano, MD, PhD, Unity Health Toronto

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

July 1, 2024

Primary Completion (Estimated)

December 1, 2025

Study Completion (Estimated)

July 1, 2026

Study Registration Dates

First Submitted

January 26, 2023

First Submitted That Met QC Criteria

January 26, 2023

First Posted (Actual)

February 6, 2023

Study Record Updates

Last Update Posted (Actual)

April 11, 2024

Last Update Submitted That Met QC Criteria

April 10, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 471164

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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