Clinical trial NCT02618382: A Study on the Safety of Tranexamic Acid for the Chronic Subdural Hematoma Population
Official title: A Study on the Safety of Tranexamic Acid for the Chronic Subdural Hematoma Population
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Subdural Hematoma
Lead sponsor: St. Joseph's Hospital and Medical Center, Phoenix
Sponsor class: OTHER
Collaborators: name: Barrow Neurological Foundation
First posted: 2015-12-01
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Medication Related (Thromboembolic) Complications
timeFrame: 30 days
Secondary outcomes:
measure: Hematoma Thickness on CT Scan
timeFrame: postoperative days 1, 3, and 30+/-7 days
measure: Functional Status Determined by Modified Rankin Score (mRS) From Baseline to 30 Days Postop
timeFrame: Measured between 2 timepoints: Baseline(Day 0) and postoperative (day 30)
measure: Change in National Institute of Health Stroke Scale (NIHSS)
timeFrame: Immediately preoperative (Day 0) and discharge (up to 30 days postoperative)
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Barrow Brain and Spine
state: Arizona
Study officials:
affiliation: Barrow Brain and Spine, Phoenix, AZ
name: Andrew S Little, MD
role: PRINCIPAL_INVESTIGATOR
References: