A Study on the Safety of Tranexamic Acid for the Chronic Subdural Hematoma Population

Phase 4

Completed

Conditions: Subdural Hematoma

Interventions: Drug: Tranexamic Acid

Registration Number: NCT02618382

Lead Sponsor: St. Joseph's Hospital and Medical Center, Phoenix

Brief Summary: 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.

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 32

Inclusion Criteria

all patients undergoing intervention for chronic subdural hematoma (cSDH) including drainage
cSDH will be defined as hematoma on CT imaging that is predominantly iso- to hypodense to brain
18-85 years of age

Exclusion Criteria

cSDH not requiring surgical drainage
patients undergoing bedside twist drill craniostomy
medically unstable for surgery
patients requiring long-term anticoagulation (unable to stay off for less than 30 days)
patients not expected to survive to the completion of followup
patients comatose prior to the initiation of treatment
history of thromboembolic problem including stroke, myocardial infarction, deep vein thrombosis and/or pulmonary embolism
pregnant
minor
allergy/sensitivity to tranexamic acid
irreversible coagulopathy
known clotting disorder
bilateral hematomas with both requiring drainage
incarcerated
any patient not judged suitable for the study by the investigators
women who are taking combination hormonal contraception

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
All subjects	Tranexamic Acid	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.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Medication Related (Thromboembolic) Complications	30 days	occurrence of stroke, myocardial infarction, deep vein thrombosis, and/or pulmonary embolism within 30 days

Secondary Outcome Measures

Name	Time	Method
Hematoma Thickness on CT Scan	postoperative days 1, 3, and 30+/-7 days	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.
Functional Status Determined by Modified Rankin Score (mRS) From Baseline to 30 Days Postop	Measured between 2 timepoints: Baseline(Day 0) and postoperative (day 30)	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. 1. The patient has no significant disability; able to resume all pre-stroke activities. 2. The patient has slight disability; unable to resume all pre-stroke activities but able to look after self without daily help. 3. The patient has moderate disability; requiring some external help but able to walk without the assistance of another individual. 4. The patient has moderately severe disability; unable to walk or attend to bodily functions without assistance. 5. The patient has severe disability; bedridden, incontinent, requires continuous care. 6. The patient has expired (during the hospital stay or after discharge from the hospital). A chi -squared test was used for categorical value
Change in National Institute of Health Stroke Scale (NIHSS)	Immediately preoperative (Day 0) and discharge (up to 30 days postoperative)	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