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| Name | Class |
|---|---|
| Barrow Neurological Foundation | OTHER |
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This is a single center single arm study of 50 patients to 1) determine the safety of tranexamic acid in the chronic subdural hematoma population following surgical drainage of chronic subdural hematomas and 2) determine if the use of oral tranexamic acid reduces the rate of ipsilateral recurrence following drainage of chronic subdural hematomas. This will be compared to historical controls. This study intends to be a prerequisite to a large nationally funded randomized control trial.
Chronic subdural hematomas are a common problem faced by neurosurgery with an annual incidence of 13.5/100,00 persons per year and up to 58/100,000 in the over 65 years old population. Their treatment is often complicated by recurrence with rates reported as high as 33%. Currently there is no good strategy to help avoid this problem, which adds significantly to patient morbidity. The pathogenesis of this problem is believed to be related to the propensity of the associated neo-membranes to bleed. It has been shown with labeled red blood cells that bleeding continues to occur into the hematoma cavity. It has also been shown that there are high levels of tissue plasminogen activator in the outer membrane of chronic subdural hematomas. It has been found that ratio of tissue plasminogen activator to plasminogen activator inhibitor contributed to the pathogenesis. It has also been shown that chronic subdural hematomas have high levels of fibrin degradation products which in addition to marking the breakdown of fibrin are themselves antihemostatic by enhancing tissue plasminogen activator activity, having an antithrombin affect and inhibiting platelet aggregation and fibrin polymerization. Essentially, a scenario of ongoing hemorrhage and repeated clot formation and hyperfibrinolysis leads to the expansion and recurrence of chronic subdural hematomas.
Given the importance of plasmin and hyperfibrinolysis in the pathophysiology of chronic subdural hematomas, interrupting its action and the vicious cycle it propagates seems an ideal therapeutic target. Tranexamic acid is a synthetic lysine amino acid derivative. It binds to the fibrin binding sites on plasmin or plasminogen and prevents its interaction and degradation of fibrin. This effect on the neo-membranes of chronic subdural hematomas should prevent rebleeding and the reaccumulation of the subdural hematoma.
Tranexamic acid has been shown to be safe and effective in reducing blood loss and transfusions in a number of types of surgery, reduced mortality and need for urgent surgery in patients with GI bleeding, and reduced bleeding associated with menorrhagia and pregnancy. Adverse effects are generally mild. Thought there is a theoretical increased risk of thromboembolic complications, multiple randomized controlled trials have not shown an increased risk. Furthermore, in a study of over 3000 gynecologic patients using tranexamic acid, there were no thromboembolic complications. This is likely because tranexamic acid has been shown to not have an effect on plasminogen in the vein wall.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| All subjects | Experimental | Patients will undergo standard treatment of their chronic subdural hematoma with the addition of preoperative and postoperative oral tranexamic acid treatment. Patients will receive a dose of 1300mg orally three to four hours prior to surgery. They will then take 1300mg orally three times daily for three days or until discharge, whichever occurs first. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tranexamic Acid | Drug | 1300mg tranexamic acid by mouth once before surgery and then three times a day for up to three days or until they are discharged from the hospital, whichever comes first |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Medication Related (Thromboembolic) Complications | occurrence of stroke, myocardial infarction, deep vein thrombosis, and/or pulmonary embolism within 30 days | 30 days |
| Measure | Description | Time Frame |
|---|---|---|
| Hematoma Thickness on CT Scan | Hematoma width (measured in cm) on post operative CT scans compared to baseline (preoperative). Preoperative axial non-contrast CT images were reviewed by a study investigator for maximal hematoma thickness, the presence of septations, and midline shift. Septations were determined to be present if there were thin, hyperdense, dividing membranes within the limits of the subdural collection. Postoperative axial non-contrast CT was planned within 24 hours post surgery and on postoperative days 3 and 30 (which could be scheduled within 7 days of the 30-day mark) to determine maximal hematoma thickness and midline shift using the preoperative methodology. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Andrew S Little, MD | Barrow Brain and Spine, Phoenix, AZ | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Barrow Brain and Spine | Phoenix | Arizona | 85013 | United States |
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Participants were recruited from a single major neurological center from Nov 2015 to Aug 2017. Patients between the ages 18 and 85 undergoing operative treatment with postop drainage of chronic SDH were evaluated for inclusion. Participants received a single dose of tranexamic acid 1300 mg preop and then 3 times daily for 3 days postop or until dc
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| ID | Title | Description |
|---|---|---|
| FG000 | All Subjects | Patients will undergo standard treatment of their chronic subdural hematoma with the addition of preoperative and postoperative oral tranexamic acid treatment. Patients will receive a dose of 1300mg orally three to four hours prior to surgery. They will then take 1300mg orally three times daily for three days or until discharge, whichever occurs first. Tranexamic Acid: 1300mg tranexamic acid by mouth once before surgery and then three times a day for up to three days or until they are discharged from the hospital, whichever comes first |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | All Subjects | Patients will undergo standard treatment of their chronic subdural hematoma with the addition of preoperative and postoperative oral tranexamic acid treatment. Patients will receive a dose of 1300mg orally three to four hours prior to surgery. They will then take 1300mg orally three times daily for three days or until discharge, whichever occurs first. Tranexamic Acid: 1300mg tranexamic acid by mouth once before surgery and then three times a day for up to three days or until they are discharged from the hospital, whichever comes first |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Medication Related (Thromboembolic) Complications | occurrence of stroke, myocardial infarction, deep vein thrombosis, and/or pulmonary embolism within 30 days | Posted | Count of Participants | Participants | 30 days |
|
at 30 days
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | All Subjects | Patients will undergo standard treatment of their chronic subdural hematoma with the addition of preoperative and postoperative oral tranexamic acid treatment. Patients will receive a dose of 1300mg orally three to four hours prior to surgery. They will then take 1300mg orally three times daily for three days or until discharge, whichever occurs first. Tranexamic Acid: 1300mg tranexamic acid by mouth once before surgery and then three times a day for up to three days or until they are discharged from the hospital, whichever comes first |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Wound infection | Infections and infestations | MedDRA (10.0) | Non-systematic Assessment | infection at site of surgical wound |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Urinary Tract Infection | Renal and urinary disorders | MedDRA (10.0) | Non-systematic Assessment |
This study limitations include its small size, lack of a control group, and deviations in study protocol with regard to postoperative imaging. Given that the study was not designed to determine the relative effectiveness of TXA in preventing recurrence, factors that may have influenced the recurrence rate, such as hematoma size, hematoma characteristics, and surgical technique, were unable to be controlled.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Lisa Arnold, Clinical Research Operations Manager | Dignity Health Research Institute | 602-406-9593 | lisa.arnold@arrowneuro.org |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Nov 9, 2017 | Oct 7, 2021 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D006408 | Hematoma, Subdural |
| ID | Term |
|---|---|
| D020198 | Intracranial Hemorrhage, Traumatic |
| D020300 | Intracranial Hemorrhages |
| D002561 | Cerebrovascular Disorders |
| D001927 | Brain Diseases |
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| ID | Term |
|---|---|
| D014148 | Tranexamic Acid |
| ID | Term |
|---|---|
| D003509 | Cyclohexanecarboxylic Acids |
| D000146 | Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
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|
| postoperative days 1, 3, and 30+/-7 days |
| Functional Status Determined by Modified Rankin Score (mRS) From Baseline to 30 Days Postop | The Modified Rankin Score (mRS) is a 6 point disability scale with scores ranging from 0 to 5. A separate category of 6 is usually added for patients who expire. Lower score of 0, 1,2 are the best outcome up to 5 with worst outcome. 0 The patient has no residual symptoms.
A chi -squared test was used for categorical value | Measured between 2 timepoints: Baseline(Day 0) and postoperative (day 30) |
| Change in National Institute of Health Stroke Scale (NIHSS) | National Institute of Health Stroke Scale (NIHSS) (0-42); 0 is better, 42 is worse. The NIHSS measures several aspects of brain function, including consciousness, vision, sensation, movement, speech, and language. A certain number of points are given for each of these physical and cognitive functions during a focused neurological examination. A maximum score of 42 represents the most severe and devastating stroke. The levels of stroke severity as measured by the NIHSS scoring system are: 0 = no stroke 1-4 = minor stroke 5-15 = moderate stroke 15-20 = moderate/severe stroke 21-42 = severe stroke | Immediately preoperative (Day 0) and discharge (up to 30 days postoperative) |
| Participants |
|
| Age, Continuous | Mean | Full Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Units | Counts |
|---|---|
| Participants |
|
|
| Secondary | Hematoma Thickness on CT Scan | Hematoma width (measured in cm) on post operative CT scans compared to baseline (preoperative). Preoperative axial non-contrast CT images were reviewed by a study investigator for maximal hematoma thickness, the presence of septations, and midline shift. Septations were determined to be present if there were thin, hyperdense, dividing membranes within the limits of the subdural collection. Postoperative axial non-contrast CT was planned within 24 hours post surgery and on postoperative days 3 and 30 (which could be scheduled within 7 days of the 30-day mark) to determine maximal hematoma thickness and midline shift using the preoperative methodology. | 1 participant did not receive 3-day post-operative follow-up CT because they were discharged home prior to day 3. 8 participants did not receive 30-day postoperative follow-up CT: in 5 of these patients, postoperative imaging was deemed unnecessary by the treating provider because of the patients' clinical progress. In the other 3 patients, follow-up imaging was obtained with magnetic resonance imaging rather than CT, as dictated by the treating surgeon | Posted | Mean | Standard Deviation | centimeters | postoperative days 1, 3, and 30+/-7 days |
|
|
|
|
| Secondary | Functional Status Determined by Modified Rankin Score (mRS) From Baseline to 30 Days Postop | The Modified Rankin Score (mRS) is a 6 point disability scale with scores ranging from 0 to 5. A separate category of 6 is usually added for patients who expire. Lower score of 0, 1,2 are the best outcome up to 5 with worst outcome. 0 The patient has no residual symptoms.
A chi -squared test was used for categorical value | Posted | Mean | Standard Deviation | score on a scale | Measured between 2 timepoints: Baseline(Day 0) and postoperative (day 30) |
|
|
|
|
| Secondary | Change in National Institute of Health Stroke Scale (NIHSS) | National Institute of Health Stroke Scale (NIHSS) (0-42); 0 is better, 42 is worse. The NIHSS measures several aspects of brain function, including consciousness, vision, sensation, movement, speech, and language. A certain number of points are given for each of these physical and cognitive functions during a focused neurological examination. A maximum score of 42 represents the most severe and devastating stroke. The levels of stroke severity as measured by the NIHSS scoring system are: 0 = no stroke 1-4 = minor stroke 5-15 = moderate stroke 15-20 = moderate/severe stroke 21-42 = severe stroke | NIHSS Assessment was not done at postoperative day 30 secondary to non in person visit. Other assessments for these 4 participants were done via telephone. | Posted | Mean | Standard Deviation | score on a scale | Immediately preoperative (Day 0) and discharge (up to 30 days postoperative) |
|
|
|
|
| 0 |
| 32 |
| 7 |
| 32 |
| 7 |
| 32 |
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| Alcohol withdrawal syndrome | Psychiatric disorders | MedDRA (10.0) | Non-systematic Assessment | Delirium tremors from alcohol withdrawal |
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| Epidural hemorrhage | Vascular disorders | MedDRA (10.0) | Non-systematic Assessment | spontaneous epidural hemorrhage |
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| seizure | Nervous system disorders | MedDRA (10.0) | Non-systematic Assessment |
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| Depressed level of consciousness | Nervous system disorders | MedDRA (10.0) | Non-systematic Assessment | Disturbances in consciousness, NEC |
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| hyponatremia | Metabolism and nutrition disorders | MedDRA (10.0) | Non-systematic Assessment | sodium less < 135 mmol/L |
|
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| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D006259 | Craniocerebral Trauma |
| D020196 | Trauma, Nervous System |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D006406 | Hematoma |
| D006470 | Hemorrhage |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D014947 | Wounds and Injuries |
|
| Postop day 3 - hematoma thickness |
|
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| Postop day 30 - hematoma hematoma thickness |
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