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

Subdural Hematoma Clinical Trial

— TXA in CSDH  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02618382
• Other study ID #: PHX15BN048
• Status: Completed
• Phase: Phase 4
• Start date: November 1, 2015
• Est. completion date: June 12, 2018

Study information

• Verified date: November 2021
• Source: St. Joseph's Hospital and Medical Center, Phoenix
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: June 12, 2018
• Est. primary completion date: August 1, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Hematoma
• Hematoma, Subdural, Chronic
• Subdural Hematoma

Intervention

Drug:
• 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

Locations

Country	Name	City	State
United States	Barrow Brain and Spine	Phoenix	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
St. Joseph's Hospital and Medical Center, Phoenix	Barrow Neurological Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
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.	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.; The patient has no significant disability; able to resume all pre-stroke activities.; The patient has slight disability; unable to resume all pre-stroke activities but able to look after self without daily help.; The patient has moderate disability; requiring some external help but able to walk without the assistance of another individual.; The patient has moderately severe disability; unable to walk or attend to bodily functions without assistance.; The patient has severe disability; bedridden, incontinent, requires continuous care.; The patient has expired (during the hospital stay or after discharge from the hospital).; A chi -squared test was used for categorical value	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	Immediately preoperative (Day 0) and discharge (up to 30 days postoperative)