Clinical trial NCT05713630: The Use of Tranexamic Acid in the Treatment of Symptomatic Subdural Hematoma
Official title: TRACE STUDY: A Randomized Controlled Trial Using Tranexamic Acid in the Treatment of Subdural Hematoma
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Subdural Hematoma
Keywords: symptomatic subdural hematoma
tranexamic acid
TXA
clinical trial
neurosurgery
Lead sponsor: Unity Health Toronto
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
name: The Physicians' Services Incorporated Foundation
First posted: 2023-02-06
Enrollment: 130
Sex: ALL
Minimum age (years): 45
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Vanguard trial
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: European Quality of Life 5 Dimensions 5 Level Version (EQ-5D-5L)
timeFrame: Every 2 weeks after randomization up to 45±10 days.
Secondary outcomes:
measure: Patient-Reported Outcomes Measurement Information System (PROMIS) Scale v1.2 - Global Health. English and French versions
timeFrame: Baseline and every 2 weeks after randomization up to 45±10 days, and then at 60-90 days, and 180±10 days after randomization.
measure: PROMIS Item Bank v2.0 - Cognitive Function. English version
timeFrame: Baseline and every 2 weeks after randomization up to 45±10 days, and then at 60-90 days, and 180±10 days after randomization.
measure: PROMIS Item Bank v2.0 - Physical Function. English version
timeFrame: Baseline and every 2 weeks after randomization up to 45±10 days, and then at 60-90 days, and 180±10 days after randomization.
measure: PROMIS Item Bank v2.0 - Ability to Participate in Social Roles and Activities. English version
timeFrame: Baseline and every 2 weeks after randomization up to 45±10 days, and then at 60-90 days, and 180±10 days after randomization.
measure: Subdural hematoma volume change
timeFrame: Baseline, 45±10 days after randomization, and 60-90 days if deemed necessary for the patient's routine care.
measure: Number of subdural hematoma-related surgical interventions
timeFrame: First admission, subsequent admissions up to 180 days after randomization
measure: Recurrence rate of SDH
timeFrame: 45±10 days, 60-90 days, and 180±10 days after randomization
measure: Mortality
timeFrame: During the course of study up to 180±10 days after randomization
measure: Modified Rankin Scale
timeFrame: Baseline, 45±10 days, 60-90 days, and 180±10 days after randomization
measure: Disability Rating Scale
timeFrame: Baseline, 45±10 days, 60-90 days, and 180±10 days after randomization
measure: Montreal Cognitive Assessment
timeFrame: Baseline, 45±10 days, and 60-90 days after randomization
measure: Medical Consumption Questionnaire
timeFrame: Baseline, 45±10 days, and 180±10 days after randomization
measure: EQ-5D-5L
timeFrame: Baseline, 60-90 days, and 180±10 days after randomization
measure: Adverse events
timeFrame: Discharge, 45±10 days, 60-90 days, and 180±10 days after randomization
measure: Length of stay in hospital due to subdural hematoma
timeFrame: During the course of the study up to 180±10 days after randomization
measure: Disposition after discharged from hospital
timeFrame: During the course of the study up to 180±10 days after randomization
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
Study officials:
affiliation: Unity Health Toronto
name: Michael D Cusimano, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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