Tranexamic Acid for Subdural Hematoma

(TRACS Trial)

Recruiting at 2 trial locations

Overseen By David Mathieu, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Centre de recherche du Centre hospitalier universitaire de Sherbrooke

Must not be taking: Anticoagulants, Hormone therapy

Disqualifiers: Thromboembolic disease, Malignancy, Pregnancy, others

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

Compensation: Varies

Number of Visits: 11

Duration: Up to 20 weeks

130 Participants Needed

Trial Summary

What is the purpose of this trial?

BACKGROUND Chronic subdural hematoma (CSDH) is one of the most frequent reasons for cranial neurosurgical consult. There is no widely accepted medical treatment for CSDH. This trial will investigate whether Tranexamic Acid (TXA) can increase the rate of CSDH resolution following conservative management, lower the number of required surgical procedures and decrease the rate of CSDH recurrence following surgical evacuation. TRACS is a double blind, randomized, parallel-design, placebo-controlled, phase IIB study designed to provide preliminary efficacy data as well as feasibility, safety and incidence data required to plan a larger definitive phase III trial. METHODS Consecutive patients presenting at the Centre Hospitalier Universitaire de Sherbrooke with a recent (\< 14 days) diagnosis of subdural hematoma with a chronic component will be screened for eligibility. Exclusion criteria include specific risk factors for thromboembolic disease, anticoagulant use or contraindication to TXA. A total of 130 patients will be randomized to receive either 750 mg of TXA daily or placebo until complete radiological resolution of the CSDH or for a maximum of 20 weeks. CSDH volume will be measured on serial CT scanning. Cognitive function tests, quality of life questionnaires as well as functional autonomy assessments will be performed at enrollment, 10 weeks follow-up and 3 months post-treatment follow-up. During the treatment period, patients will undergo standard CSDH management with surgery being performed at the discretion of the treating physician. If surgery is performed, the CSDH and its outer membrane will be sampled for in vitro analysis. The primary outcome is the rate of CSDH resolution at 20 weeks without intervening unplanned surgical procedure. Secondary outcomes include CSDH volume, incidence of surgical evacuation procedures, CSDH recurrence, cognitive functions, functional autonomy, quality of life, incidence of complications and length of hospital stay. Planned subgroup analyses will be performed for conservatively vs surgically-managed subjects and highly vs poorly vascularised CSDH. DISCUSSION CSDH is a frequent and morbid condition for which an effective medical treatment has yet to be discovered. The TRACS trial will be the first prospective study of TXA for CSDH.

Will I have to stop taking my current medications?

The trial requires that you stop taking anticoagulant medications to participate. If you are on such medications, you would need to discontinue them before joining the trial.

What data supports the effectiveness of the drug Tranexamic Acid (TXA) for subdural hematoma?

Research on Tranexamic Acid (TXA) for chronic subdural hematomas (CSDH) shows mixed results. While some studies suggest TXA might help reduce recurrence rates after surgery, others indicate it may not be effective and could increase complications. Additionally, TXA has been shown to reduce mortality in patients with mild to moderate traumatic brain injuries, which may suggest potential benefits in similar conditions. ^{1 2 3 4 5}

Is tranexamic acid generally safe for humans?

Tranexamic acid (TXA) has been used in various medical conditions, but in a study on chronic subdural hematoma, it was associated with a higher rate of complications compared to a control group. While the study was small, it suggests that TXA might increase the odds of complications in this context. ^{1 2 3 4 6}

How does the drug tranexamic acid differ from other treatments for subdural hematoma?

Tranexamic acid (TXA) is unique because it is an antifibrinolytic agent, meaning it helps prevent the breakdown of blood clots, which may reduce the recurrence of subdural hematomas. Unlike other treatments that often involve surgery, TXA offers a potential non-surgical option for managing this condition. ^{2 3 4 7 8}

Research Team

David Mathieu, M.D.

Principal Investigator

Université de Sherbrooke

Eligibility Criteria

This trial is for patients recently diagnosed (within the last 14 days) with chronic subdural hematoma. It's not suitable for those with acute hematomas, thrombotic diseases, recent strokes or heart surgeries, active cancer treatments, certain genetic disorders related to blood clotting, or women who are pregnant/breastfeeding.

Inclusion Criteria

You have a long-lasting collection of blood outside the brain.

Diagnosis within the last 14 days

Exclusion Criteria

You have a metal heart valve.

I have a recent brain bleed without any old bleeding.

I have a genetic condition that increases my risk of blood clots.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

1 visit (in-person)

Treatment

Participants receive either 750 mg of Tranexamic Acid daily or placebo until complete radiological resolution of the CSDH or for a maximum of 20 weeks

Up to 20 weeks

Regular visits for CT scans and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment, including cognitive function tests, quality of life questionnaires, and functional autonomy assessments

12 weeks

Follow-up visits at 10 weeks and 3 months post-treatment

Treatment Details

Interventions

• Placebo
• Tranexamic Acid

Trial Overview The study tests if Tranexamic Acid can help resolve chronic subdural hematomas without surgery and prevent recurrence after surgical treatment. Participants will receive either TXA or a placebo alongside standard care in this double-blind phase IIB trial.

Participant Groups

Group I: Tranexamic acid Experimental Treatment 1 Intervention

Tranexamic acid 750 mg daily until complete radiological resolution of the chronic subdural hematoma or a maximum of 20 weeks.

Group II: Placebo Placebo Group 1 Intervention

Placebo tablet daily until complete radiological resolution of the chronic subdural hematoma or a maximum of 20 weeks.

Who Is Running the Clinical Trial?

Centre de recherche du Centre hospitalier universitaire de Sherbrooke

Lead Sponsor

Trials

64

Recruited

33,600+

Université de Sherbrooke

Collaborator

Trials

317

Recruited

79,300+

Findings from Research

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]

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 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 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]

The CRASH-3 trial found that tranexamic acid (TXA) significantly reduces mortality in patients with mild to moderate traumatic brain injuries associated with intracranial bleeding.

Despite its promising results, the limitations of the trial prevent TXA from being established as the gold standard treatment for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tranexamic acid and traumatic brain injuries. Sanford, K., Garcia, S.[2021]

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]

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]

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. 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]

2. England pubmed.ncbi.nlm.nih.gov

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

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

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

4. 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]

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

Tranexamic acid and traumatic brain injuries. [2021]

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

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

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

Tranexamic acid for chronic subdural hematoma. [2022]