Tranexamic Acid for Subdural Hematoma

(TRACE Trial)

Overseen By Melissa C Fazari, MSc

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Michael Cusimano

Must not be taking: Birth control, Hormonal therapy, Anticoagulants, others

Disqualifiers: Pregnancy, Renal insufficiency, Malignancy, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 45

Duration: 45 days

130 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but you cannot participate if you need to continue taking certain blood thinners or anticoagulants like warfarin or direct oral anticoagulants for two weeks after surgery.

What data supports the effectiveness of the drug Tranexamic Acid for treating subdural hematoma?

Some studies suggest that Tranexamic Acid (TXA) might help reduce the recurrence of chronic subdural hematomas after surgery, but the evidence is not strong, and there may be an increased risk of complications. Therefore, its effectiveness for this condition is still uncertain. ^{1 2 3 4 5}

Is tranexamic acid generally safe for use in humans?

Tranexamic acid (TXA) has been studied for various conditions, including brain injuries and chronic subdural hematomas. Some studies suggest it may increase the risk of complications, but overall, it has been used in many patients without significant safety concerns. However, more research is needed to fully understand its safety profile. ^{3 4 5 6 7}

How is the drug Tranexamic Acid unique in treating subdural hematoma?

Tranexamic Acid (TXA) is unique because it is an antifibrinolytic agent, meaning it helps prevent the breakdown of blood clots, which can reduce the recurrence and size of subdural hematomas. Unlike other treatments that often involve surgery, TXA offers a non-surgical option for managing this condition. ^{1 2 3 5 8}

Research Team

Michael Cusimano, MD, MHPE, FRCS, PhD

Principal Investigator

Unity Health Toronto

Eligibility Criteria

This trial is for individuals aged 45 and older, weighing between 45-150 kg, diagnosed with symptomatic subdural hematoma (SDH) of at least 8 mm thickness. Participants must have symptoms like headaches or confusion due to SDH but cannot be in a rapidly deteriorating state or have certain other brain injuries, severe kidney issues, known bleeding disorders, recent malignancies, or be pregnant.

Inclusion Criteria

I have SDH and experience symptoms like headaches, confusion, or seizures.

I am 45 or older, weigh between 45-150 kg, and have been diagnosed with symptomatic SDH.

I have a significant blood clot in my brain, shown on a CT scan.

Exclusion Criteria

Known acquired colour vision disturbances

SDH less than 8 mm in maximal thickness

Mechanical heart valve

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive either Tranexamic Acid (TXA) or placebo for 45 days, with a loading dose followed by regular doses

45 days

Regular monitoring visits as per study protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments at multiple time points

Up to 180 days

Visits at 45±10 days, 60-90 days, and 180±10 days

Treatment Details

Interventions

• Tranexamic Acid

Trial Overview The study tests Tranexamic Acid (TXA), which helps prevent blood clots from breaking down to reduce further bleeding in SDH patients. Some participants will receive TXA while others will get a placebo. The goal is to see if TXA can lower the chance of rebleeding post-surgery and improve recovery without additional surgeries.

Participant Groups

Group I: Standard care + TXA Active Control 1 Intervention

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.

Group II: Standard care + placebo Placebo Group 1 Intervention

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.

Tranexamic Acid is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Tranexamic Acid for:

• Heavy menstrual bleeding
• Prevention of excessive bleeding during surgeries

Approved in European Union as Tranexamic Acid for:

• Heavy menstrual bleeding
• Prevention of excessive bleeding during surgeries
• Hereditary angioedema

Approved in Canada as Tranexamic Acid for:

• Heavy menstrual bleeding
• Prevention of excessive bleeding during surgeries

Approved in Japan as Tranexamic Acid for:

• Heavy menstrual bleeding
• Prevention of excessive bleeding during surgeries

Who Is Running the Clinical Trial?

Michael Cusimano

Lead Sponsor

Trials

1

Recruited

130+

Unity Health Toronto

Lead Sponsor

Trials

572

Recruited

470,000+

Ozmosis Research Inc.

Industry Sponsor

Trials

25

Recruited

5,200+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

The Physicians' Services Incorporated Foundation

Collaborator

Trials

165

Recruited

31,700+

Applied Health Research Centre

Collaborator

Trials

23

Recruited

70,900+

Findings from Research

In a study of 240 patients with chronic subdural hematoma (CSDH), the use of tranexamic acid (TXA) as an adjunctive treatment significantly accelerated the resolution of the hematoma, with a median resolution time that was notably faster compared to those not receiving TXA (p<0.001).

The recurrence rate of CSDH was lowest in the TXA group at 2.4%, suggesting that TXA may help reduce the chances of hematoma re-accumulation, although the difference was not statistically significant due to the small number of recurrences.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of Adjunctive Tranexamic Acid in Facilitating Resolution of Chronic Subdural Hematoma after Surgery. Yang, K., Kim, KH., Lee, HJ., et al.[2023]

In a three-year study involving 27 patients with chronic subdural hematoma (CSDH), treatment with tranexamic acid (Txa) at a dosage of 750 mg/day resulted in good resolution of hematomas without any complications.

The study suggests that Txa is a safe and effective conservative management option for CSDH in patients who are relatively and mildly symptomatic, as none of the hematomas progressed during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Outcome of Medical Management of Chronic Subdural Hematoma with Tranexamic Acid - A Prospective Observational Study. Kutty, RK., Leela, SK., Sreemathyamma, SB., et al.[2021]

The TRACS trial is a multicenter, double-blind study involving 130 patients to evaluate the efficacy of Tranexamic Acid (TXA) in promoting the resolution of chronic subdural hematomas (CSDH) without the need for surgery, aiming for results within 20 weeks.

This trial will assess not only the rate of CSDH resolution but also the impact of TXA on surgical intervention rates, recurrence, cognitive function, and quality of life, making it a comprehensive approach to understanding TXA's potential benefits in managing CSDH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tranexamic Acid in Chronic Subdural Hematomas (TRACS): study protocol for a randomized controlled trial. Iorio-Morin, C., Blanchard, J., Richer, M., et al.[2022]

In a randomized controlled trial involving 50 patients with chronic subdural hematoma, the use of tranexamic acid (TXA) post-surgery did not significantly reduce the recurrence rate of hematomas compared to the control group.

The TXA group experienced a higher recurrence rate (8.3%) and had two postoperative complications, suggesting that TXA may not be beneficial and could potentially increase the risk of complications in patients undergoing treatment for chronic subdural hematoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of postoperative tranexamic acid on recurrence rate and complications in chronic subdural hematomas patients: preliminary results of a randomized controlled clinical trial. de Paula, MVCT., Ribeiro, BDC., Melo, MM., et al.[2023]

In a study of 6647 elderly patients who underwent burr hole craniotomy for chronic subdural hematoma, oral administration of tranexamic acid (TXA) significantly reduced the need for repeat surgery, with only 6.5% of patients in the TXA group requiring a second procedure compared to 16.8% in the control group.

The use of TXA did not increase the risk of death or thrombosis, indicating that it is a safe option for preventing postoperative recurrence in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Administration of Tranexamic Acid After Burr Hole Craniotomy Reduced Postoperative Recurrence of Chronic Subdural Hematoma in a Japanese Regional Population. Miyakoshi, A., Nakatani, E., Kaneda, H., et al.[2023]

Tranexamic acid (TXA) significantly reduces the risk of rebleeding and mortality from rebleeding in patients with aneurysmal subarachnoid hemorrhage (aSAH), based on a meta-analysis of 13 studies involving 2991 patients.

Despite its benefits in reducing rebleeding, TXA does not improve overall mortality, neurological outcomes, delayed cerebral ischemia, or hydrocephalus, and no significant adverse events were reported, indicating it is a safe intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tranexamic acid for patients with aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis of 2991 patients. Ghaith, HS., Gabra, MD., Ebada, MA., et al.[2022]

Tranexamic acid (TXA) significantly reduces the rate of hematoma expansion in patients with traumatic brain injury (TBI), which can lead to lower mortality rates and improved neurologic outcomes, based on a systematic review of 5 randomized controlled trials involving 917 patients.

The effectiveness of TXA is enhanced when treatment is administered early, and it does not increase the risk of thrombosis events, indicating it is a safe option for managing hemorrhage in TBI patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Tranexamic Acid in Patients with Traumatic Brain Injury: A Systematic Review and Meta-Analysis. Weng, S., Wang, W., Wei, Q., et al.[2019]

In a study of seven patients with chronic subdural hematoma (cSDH) treated with tranexamic acid (TXA), five patients showed complete resolution of symptoms, suggesting TXA may be an effective conservative treatment for mild cases.

The median hematoma volume decreased by 73% in non-operated patients after TXA treatment, indicating a significant reduction in the size of the hematoma, although one patient required surgery due to worsening symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tranexamic acid for chronic subdural hematoma. Lodewijkx, R., Immenga, S., van den Berg, R., et al.[2022]

References

1. Korea (South) pubmed.ncbi.nlm.nih.gov

Role of Adjunctive Tranexamic Acid in Facilitating Resolution of Chronic Subdural Hematoma after Surgery. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

The Outcome of Medical Management of Chronic Subdural Hematoma with Tranexamic Acid - A Prospective Observational Study. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Tranexamic Acid in Chronic Subdural Hematomas (TRACS): study protocol for a randomized controlled trial. [2022]

4. Germany pubmed.ncbi.nlm.nih.gov

Effect of postoperative tranexamic acid on recurrence rate and complications in chronic subdural hematomas patients: preliminary results of a randomized controlled clinical trial. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Administration of Tranexamic Acid After Burr Hole Craniotomy Reduced Postoperative Recurrence of Chronic Subdural Hematoma in a Japanese Regional Population. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Tranexamic acid for patients with aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis of 2991 patients. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Effect of Tranexamic Acid in Patients with Traumatic Brain Injury: A Systematic Review and Meta-Analysis. [2019]

8. England pubmed.ncbi.nlm.nih.gov

Tranexamic acid for chronic subdural hematoma. [2022]