Tranexamic Acid in the Treatment of Residual Chronic Subdural Hematoma (TRACE)

Tranexamic Acid in the Treatment of Residual Chronic Subdural Hematoma: A Single-centre, Observer-blinded, Randomized Controlled Trial.

Chronic subdural hematoma (CSDH) is a common disease after minor head trauma, especially in elderly patients. This medical condition is characterized by blood collection in the subdural space, which can result in severe neurological impairment. Current standard of care is the evacuation of the CSDH by means of different surgical approaches. Although clinical and surgical outcomes are satisfying in most cases, considerable morbidity and mortality as well as recurrence rates of 3-31% are frequently reported. Therefore a non-surgical approach for the treatment of CSDH would be desirable. Tranexamic acid (TXA), an antifibrinolytic drug has been shown to decrease hematoma volume in a small cohort of patients suffering from CSDH. The present study is designed to test the hypothesis that TXA can reduce the volume of CSDH. Volume measurements of residual CSDH after burr-hole surgery will be performed during study course to quantify treatment success. The trial is designed as a randomized controlled pilot study, where half of the patients will be assigned to daily intake of TXA, whereas the other half will receive medical treatment according to current practice without TXA prescription. The primary endpoint of the study is defined as volume change in milliliters (mL) after 4-8 weeks of treatment. Secondary endpoints are hematoma volume change at 8-12 weeks, the rate of patients with resolution of the CSDH after 4-8 weeks and 8-12 weeks days, as well as the rate of reoperation during study course due to hematoma extension and neurological deterioration. Additionally the neurological outcome and the drug compatibility will be estimated as secondary objectives.

Study Overview

• Status: Unknown
• Conditions: Chronic Subdural Hematoma
• Intervention / Treatment: Drug: Tranexamic Acid 500 MG

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5B 1W8
      • Recruiting
      • St. Michael's Hospital
      • Contact: Adriana M Workewych, HBSc; Phone Number: 416-864-5312; Email: workewycha@smh.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients diagnosed with chronic subdural hematoma, and have a planned or have received a unilateral or bilateral burr-hole craniostomy or mini-craniotomy
• Written informed consent (patient, power of attorney or substitute decision maker)
• Competence to take study medication properly and regularly or access to care giver that is able to comply with accurate study medication administration

Exclusion Criteria:

• Hypersensitivity to TXA or any of the ingredients
• Pregnancy
• Irregular menstrual bleeding with unidentified cause
• Acquired colour vision disturbances
• Acute and chronic renal insufficiency indicated by glomerular filtration rate (GFR) ≤ 30 mL/min
• Hematuria, caused by diseases of renal parenchyma
• Current alcohol abuse (as indicated by an Alcohol Use Disorders Identification Test (AUDIT) score of 10 or higher) drug abuse, or recreational drug use
• Concomitant intake of hormonal contraceptives, factor IX complex concentrates, and anti-inhibitor coagulant concentrates (factor VII, activated factor IX)
• Active, history, or increased risk of thrombotic events (including deep vein thrombosis, pulmonary embolism, cerebral venous thrombosis, arterial thrombotic events), symptomatic carotid stenosis, myocardial infarction, acute coronary syndrome, coronary artery disease, or consumption coagulopathy within the past 2 years
• History of angioplasty with cardiac stent placement or mechanical heart valve
• Active or history of brain pathologies such as stroke (hemorrhagic and ischemic), subarachnoid hemorrhage, or malignant brain tumors (glioma, metastasis and others) as well as history of seizures within the past 2 years
• Contraindication to stopping full therapeutic doses of non-acetylsalicylic acid (ASA) antiplatelets, warfarin, rivaroxaban, apixaban, dabigatran, or other anticoagulant for 2 weeks after surgery
• Patients requiring immediate revision surgery (as defined by attending surgeon)
• Inability of oral drug intake or missing support to guarantee oral drug intake

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tranexamic Acid Arm; Tranexamic Acid 500 milligrams (MG) Participants of the Tranexamic Acid (TXA) arm will receive the study drug, TXA. Participants of average body weight (60-100kg) will receive TXA according to a 500mg three times daily (TID) dose regimen. Weight deviations from this range will see dose adjustments as follows: participants <60kg will receive 500mg two times daily (BID), and participants >100kg will receive 1000mg BID.	Drug: Tranexamic Acid 500 MG; Tranexamic Acid 500mg oral tablets.; Other Names: TXA
No Intervention: Control Arm; No intervention Participants in the control arm will not receive any additional intervention, medication, or placebo, and will serve as a comparative arm for the experimental arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Chronic subdural hematoma volume change	Change in hematoma volume in mL according to volume measurements made on CT scans comparing CT scan at 4-8 weeks to immediate post-operative CT scan.	4-8 weeks, 8-12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neurological outcome	An assessment of neurological outcome as measured by the National Institutes of Health Stroke Scale (NIHSS)	4-8 weeks, 8-12 weeks
Quality of life	Participants quality of life as measured on the Health Utilities Index (HUI).	4-8 weeks, 8-12 weeks
Quality of life	Participants quality of life as measured on the 36-item Short Form Health Survey (SF-36).	4-8 weeks, 8-12 weeks
Occurrence of adverse events	Safety of the TXA dose regimen by monitoring incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]	4-8 weeks, 8-12 weeks

Collaborators and Investigators

• Sponsor: Unity Health Toronto

Study record dates

Study Major Dates

• Study Start (Actual): March 6, 2017
• Primary Completion (Anticipated): March 1, 2018
• Study Completion (Anticipated): March 1, 2018

Study Registration Dates

• First Submitted: September 10, 2017
• First Submitted That Met QC Criteria: September 11, 2017
• First Posted (Actual): September 12, 2017

Study Record Updates

• Last Update Posted (Actual): September 14, 2017
• Last Update Submitted That Met QC Criteria: September 13, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: Tranexamic acid; Chronic subdural hematoma; TXA
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Hemorrhage; Craniocerebral Trauma; Trauma, Nervous System; Intracranial Hemorrhages; Intracranial Hemorrhage, Traumatic; Hematoma; Hematoma, Subdural; Hematoma, Subdural, Chronic; Molecular Mechanisms of Pharmacological Action; Fibrin Modulating Agents; Antifibrinolytic Agents; Hemostatics; Coagulants; Tranexamic Acid
• Other Study ID Numbers: 14-0176-GAP

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No