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

• ClinicalTrials.gov Identifier: NCT02618382
• Recruitment Status: Unknown
• First Posted: December 1, 2015
• Last Update Posted: December 13, 2016
• Sponsor: St. Joseph's Hospital and Medical Center, Phoenix
• Collaborator: Barrow Neurological Foundation
• Information provided by (Responsible Party): Madelon Petersen, St. Joseph's Hospital and Medical Center, Phoenix

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Subdural Hematoma	Drug: Tranexamic Acid	Phase 4

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 50 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Study Start Date: November 2015
• Estimated Primary Completion Date: June 2017
• Estimated Study Completion Date: January 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: 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.	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; Other Names: Lysteda; Cyklokapron

Outcome Measures

Primary Outcome Measures :

1. Medication Related Complications [ Time Frame: 30 days ]
   occurrence of stroke, myocardial infarction, deep vein thrombosis, and/or pulmonary embolism

Secondary Outcome Measures :

1. Postoperative hematoma expansion assessed by preoperative CT comparing width of hematoma to postoperative CTs [ Time Frame: postoperative days 1, 3, 7, and 30+/-7 days ]
   preoperative CT comparing width of hematoma to postoperative CTs
2. Modified Rankin Scale (mRS) [ Time Frame: preoperative (Day 0) and postoperative (day 30) ]
   postoperative score will equal or exceed preoperative score
3. National Institute of Health Stroke Scale (NIHSS) [ Time Frame: immediately preoperative (Day 0) and discharge (up to 30 days postoperative) ]
   postoperative score will equal or exceed preoperative score

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 85 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Contacts

Contact: Heidi Jahnke, RN, MSN; 602-406-6976; heidi.jahnke@dignityhealth.org

Locations

United States, Arizona

Barrow Brain and Spine; Recruiting

Phoenix, Arizona, United States, 85013

Contact: Heidi Jahnke, RN, MSN 602-406-6976 heidi.jahnke@dignityhealth.org

Principal Investigator: Andrew S Little, MD

Sub-Investigator: Rami Almefty, MD

Sponsors and Collaborators

St. Joseph's Hospital and Medical Center, Phoenix

Barrow Neurological Foundation

Investigators

• Principal Investigator: Andrew S Little, MD; Barrow Brain and Spine, Phoenix, AZ

More Information

• Responsible Party: Madelon Petersen, Investigator, St. Joseph's Hospital and Medical Center, Phoenix
• ClinicalTrials.gov Identifier: NCT02618382
• Other Study ID Numbers: PHX15BN048
• First Posted: December 1, 2015
• Last Update Posted: December 13, 2016
• Last Verified: December 2016

Additional relevant MeSH terms:

Hematoma, Subdural; Hematoma; Hemorrhage; Pathologic Processes; Intracranial Hemorrhage, Traumatic; Intracranial Hemorrhages; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Vascular Diseases; Cardiovascular Diseases; Wounds and Injuries; Tranexamic Acid; Antifibrinolytic Agents; Fibrin Modulating Agents; Molecular Mechanisms of Pharmacological Action; Hemostatics; Coagulants