Tranexamic Acid in Chronic Subdural Hematomas

Study Overview
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Brief Summary
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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.

Official Title
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Tranexamic Acid in Chronic Subdural Hematomas

Conditions
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Chronic Subdural Hematoma

Intervention / Treatment
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* Drug: Tranexamic Acid
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: CT scan demonstrating the existence of a subdural hematoma containing a chronic component Diagnosis within the last 14 days Exclusion Criteria: Acute subdural hematoma with no chronic component; Active thrombotic, thromboembolic or atheroembolic disease, including deep venous thrombosis within the last six months, cerebral thrombosis within the last six months, symptomatic carotid stenosis who did not undergo surgery or stroke within the last year; Past history of unprovoked deep venous thrombosis or idiopathic pulmonary embolism; Known hereditary thrombophilia, including Factor V Leiden, Antithrombin III mutation, Protein C deficiency, Protein S deficiency; Atrial fibrillation (unless under successful rhythm control therapy); Metallic heart valve; Vascular stenting procedure within the last year; Cardiac or vascular surgical procedure within the last 6 months, including endarterectomy, bypass or angioplasty; Ongoing investigation for suspected malignancy; Confirmed active malignancy; Concomitant hormone therapy for malignancy; Concomitant hormone contraceptive pill; Macroscopic hematuria; Known or suspected tranexamic acid allergy; Pregnancy or breastfeeding; Concomitant use of anticoagulant medication; Any concern from the attending physician.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tranexamic acid<br>Tranexamic acid 750 mg daily until complete radiological resolution of the chronic subdural hematoma or a maximum of 20 weeks. | Drug: Tranexamic Acid<br> <br> * Other names: Cyklokapron;|
| Placebo Comparator: Placebo<br>Placebo tablet daily until complete radiological resolution of the chronic subdural hematoma or a maximum of 20 weeks. | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hematoma resolution | The rate of chronic subdural hematoma resolution without intervening unplanned surgical procedure. Specifically, if the initial management strategy chosen by the attending physician within the first 24 hours of presentation consists of expectant management, any surgical procedure leads to a failure of meeting the primary outcome. On the other hand, if the management strategy chosen by the attending physician within the first 24 hours of presentation included a surgical evacuation of the CSDH, the primary outcome is met if the control CT scan at 20 weeks demonstrates a complete radiological resolution of the CSDH. Should a second surgery be required, the subject will fail to meet the primary outcome even if the CSDH has completely resolved by 20 weeks. | 20 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hematoma volume | Measured by segmentation analysis on the 20 weeks CT scan | 20 weeks | 
| Surgical evacuation | The incidence of surgical evacuation procedures | 32 weeks | 
| Hematoma recurrence |  | 32 weeks | 
| Cognitive function | Assessed by the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE) | 10 weeks | 
| Cognitive function | Assessed by the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE) | 32 weeks | 
| Functional autonomy | Assessed by the modified Barthel Index (mBI) and Glasgow Outcome Scale Extended (GOSE) | 10 weeks | 
| Functional autonomy | Assessed by the modified Barthel Index (mBI) and Glasgow Outcome Scale Extended (GOSE) | 32 weeks | 
| Quality of life scores at 10 weeks | Assessed by the EQ-5D-5L and the Sherbrooke Neuro-oncology Assessment Scale (SNAS) | 10 weeks | 
| Quality of life scores at 32 weeks | Assessed by the EQ-5D-5L and the Sherbrooke Neuro-oncology Assessment Scale (SNAS) | 32 weeks | 
| Length initial of hospital stay |  | 32 weeks | 
| Number of rehospitalisation |  | 32 weeks | 
| Complications | Incidence of any complication related to tranexamic acid administration | 32 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tranexamic acid, Cyklokapron, Conservative management, Medical management