Tranexamic Acid in the Treatment of Residual Chronic Subdural Hematoma -2

Study Overview
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Brief Summary
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Chronic subdural hematoma (CSDH), a common disease after minor head trauma, is characterized by blood collection in the subdural space, which can result in severe neurological impairment. The current standard of care is the surgical evacuation of CSDH. Although clinical and surgical outcomes are satisfying in most cases, considerable morbidity, mortality and recurrence rates of 3-31% are frequently reported. Therefore a non-surgical approach to treat CSDH is desirable. Tranexamic acid (TXA), an antifibrinolytic drug, has been shown to decrease hematoma volume in a small cohort of CSDH patients. The present study is designed to test the hypothesis that TXA can reduce the volume of CSDH. Volume measurements of residual CSDH after burr-hole surgery will be performed to quantify treatment success. The trial is designed as a double-blinded randomized controlled trial, where half of the patients will be assigned to daily intake of TXA, whereas the other half will receive placebo. The primary endpoint is defined as volume change in milliliter after 4-8 weeks of treatment. Secondary endpoints are hematoma volume at 8-12 weeks, patient safety, the number of patients with resolution of the CSDH after 4-8 and 8-12 weeks of study participation, the neurological outcome, the rate of reoperation, the time to reoperation, drug safety and compatibility, and participant quality of life (QOL).

Official Title
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Tranexamic Acid in the Treatment of Residual Chronic Subdural Hematoma: An Observer-blinded, Randomized Controlled Trial

Conditions
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Chronic Subdural Hematoma

Intervention / Treatment
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* Drug: Tranexamic Acid 500 MG
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of chronic subdural hematoma (CSDH) Written informed consent (patient, power of attorney or substitute decision maker) Competence to take study medication properly and regularly or access to caregiver that is able to comply with accurate study medication administration Exclusion Criteria: Hypersensitivity to TXA or any of the ingredients Pregnancy Irregular menstrual bleeding with unidentified cause Acquired colour vision disturbances Acute and chronic renal insufficiency indicated by GFR ≤ 30 mL/min Hematuria, caused by diseases of renal parenchyma Concomitant intake of hormonal contraceptives, factor IX complex concentrates, and anti-inhibitor coagulant concentrates (factor VII, activated factor IX) History of angioplasty with cardiac stent placement, or cardiac (including mechanical) valve placement Active history of stroke (hemorrhagic and ischemic), or subarachnoid hemorrhage, within the past 6 months Consumption coagulopathy/disseminated intravascular coagulation (DIC) in the last 7 days History of malignant brain tumors (glioma, metastasis and others) or seizures within the 6 months Contraindication to stopping full therapeutic doses of non-ASA antiplatelets, warfarin, rivaroxaban, apixaban, dabigatran, or other anticoagulant for 2 weeks after surgery Inability of oral drug intake or missing support to guarantee oral drug intake SDH as caused by intracranial hypotension resulting from CSF shunt placement

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tranexamic Acid Arm<br>Participants in the experimental arm will receive tranexamic acid (TXA) during surgery for CSDH evacuation with a single 1000mg intraoperative intravenous (IV) dose. Participants with a body weight 60-100kg will also receive a post-operative dose regimen of 500 mg TXA orally, 3 times a day (TID). Weight deviations from this body weight range will be considered with a dose adjustment of 1000mg TXA two times a day (BID) for a body weight >100 kg, and 500 mg TXA BID for body weight <60kg. | Drug: Tranexamic Acid 500 MG<br>* Tranexamic Acid 500mg oral tablets<br>|
| Placebo Comparator: Placebo Control Arm<br>Participants in the control arm will placebo according to the same administration regimen. | Drug: Placebo<br>* The placebo will consist of an identical capsule to over-encapsulated tranexamic acid oral tablet entirely filled with microcrystalline cellulose, and sealed.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Chronic subdural hematoma volume change | Change in hematoma volume in mL according to CT-scan-based volume measurements comparing hematoma on CT scan performed at 4-8 weeks to hematoma on immediate post-operative CT scan. | At 4-8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Chronic subdural hematoma volume change | Change in hematoma volume in mL according to CT-scan-based volume measurements comparing hematoma on CT scan performed at 4-8 weeks to hematoma on immediate post-operative CT scan. | At 12 weeks | 
| Rate of adverse events (AEs) | Adverse events investigated include: suspected stroke myocardial infarction deep vein thrombosis thromboembolic events decline in renal function new-onset neurological deterioration Serious adverse events include: evidence of stroke myocardial infarction deep vein thrombosis thromboembolic events convulsions severe allergic reactions evidence of retinal degeneration necessity of hospital admission mortality | At 4, 8, and 12 weeks | 
| 36-Item Short Form Survey (SF-36) | Questionnaire assessing patient quality of life outcome profile | At 4, 8, 12 weeks | 
| National Institutes of Health Stroke Scale (NIHSS) | Change in National Institutes of Health Stroke Scale (NIHSS) score (neurological outcome) at 4-8 weeks and 8-12 weeks, compared to the baseline visit score Minimum scale score: 0; Maximum scale score: 42. Higher score means worse neurological impairment. | At 4, 8, and 12 weeks | 
| Modified Rankin Scale (mRS) | Change in Modified Rankin Scale (mRS) score (neurological outcome) at 4-8 weeks and 8-12 weeks, compared to the baseline visit score Minimum scale score: 0 (no symptoms); Maximum scale score: 6 (death). Higher score means worse neurological outcome. | At 4, 8, and 12 weeks | 
| Markwalder's grading scale (MGS) | Change in Markwalder's grading scale (MGS) score (neurological outcome) at 4-8 weeks and 8-12 weeks, compared to the baseline visit score Minimum scale score: 0 (normal); Maximum scale score: 4. Higher score means worse neurological outcome. | At 4, 8, and 12 weeks | 
| Rate of re-operation | Rate of re-operation during study course due to hematoma enlargement or other significant cause | At 4, 8, and 12 weeks | 
| Time to reoperation | Time to reoperation during study course due to hematoma enlargement or other significant cause | At 4, 8, and 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tranexamic acid, Chronic Subdural Hematoma, Neurosurgery