The Use of Tranexamic Acid in the Treatment of Symptomatic Subdural Hematoma

Phase 3

Not yet recruiting

• Conditions: Subdural Hematoma
• Interventions: Drug: Placebo; Drug: Tranexamic acid (TXA)

• Registration Number: NCT05713630
• Lead Sponsor: Unity Health Toronto

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-01-26
• Study First Submitted QC: 2023-01-26
• Study First Posted: 2023-02-06
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-25
• Last Update Posted: 2025-03-30
• Study Start: 2025-06-01
• Primary Completion: 2030-03-01
• Study Completion: 2030-11-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 130

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard care + placebo	Placebo	Patients will be given a single oral or IV loading dose of placebo within three hours of being randomized or 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%) 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 500mg placebo by mouth (or IV for those unable to swallow) three times a day, totalling 1500mg/day, for 45 days.
Standard care + TXA	Tranexamic acid (TXA)	Patients will be given a single oral or IV loading dose of TXA within three hours of being randomized or 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 as per the recommended rate of administration in the Product Monograph for Sandoz-Tranexamic Acid Injection BP. After 12 hours of the loading dose, patients will be given 500mg TXA by mouth (or 500mg TXA in NaCl 0.9% 100mL by IV for those unable to swallow) three times daily, totalling 1500mg/day, for 45 days.

Primary Outcome Measures

Name	Time	Method
European Quality of Life 5 Dimensions 5 Level Version (EQ-5D-5L)	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.

Secondary Outcome Measures

Name	Time	Method
Patient-Reported Outcomes Measurement Information System (PROMIS) Scale v1.2 - Global Health. English and French versions	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.
Disability Rating Scale	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.
PROMIS Item Bank v2.0 - Cognitive Function. English version	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.
Mortality	During the course of study up to 180±10 days after randomization
Modified Rankin Scale	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.
PROMIS Item Bank v2.0 - Physical Function. English version	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.
Number of subdural hematoma-related surgical interventions	First admission, subsequent admissions up to 180 days after randomization
Adverse events	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.
EQ-5D-5L	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.
PROMIS Item Bank v2.0 - Ability to Participate in Social Roles and Activities. English version	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.
Subdural hematoma volume change	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.
Recurrence rate of SDH	45±10 days, 60-90 days, and 180±10 days after randomization
Montreal Cognitive Assessment	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.
Medical Consumption Questionnaire	Baseline, 45±10 days, and 180±10 days after randomization	Health-related cost questionnaire on the use of healthcare in the past month.
Disposition after discharged from hospital	During the course of the study up to 180±10 days after randomization
Length of stay in hospital due to subdural hematoma	During the course of the study up to 180±10 days after randomization

Trial Locations

Locations (1)

St. Michael's Hospital; 🇨🇦 Toronto, Ontario, Canada