Tranexamic Acid in the Treatment of Residual Chronic Subdural Hematoma -2 (TRACE-2)

Tranexamic Acid in the Treatment of Residual Chronic Subdural Hematoma: An Observer-blinded, Randomized Controlled Trial

Chronic subdural hematoma (CSDH), a common disease after minor head trauma, is characterized by blood collection in the subdural space, which can result in severe neurological impairment. The current standard of care is the surgical evacuation of CSDH. Although clinical and surgical outcomes are satisfying in most cases, considerable morbidity, mortality and recurrence rates of 3-31% are frequently reported. Therefore a non-surgical approach to treat CSDH is desirable. Tranexamic acid (TXA), an antifibrinolytic drug, has been shown to decrease hematoma volume in a small cohort of CSDH patients. 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 to quantify treatment success. The trial is designed as a double-blinded randomized controlled trial, where half of the patients will be assigned to daily intake of TXA, whereas the other half will receive placebo. The primary endpoint is defined as volume change in milliliter after 4-8 weeks of treatment. Secondary endpoints are hematoma volume at 8-12 weeks, patient safety, the number of patients with resolution of the CSDH after 4-8 and 8-12 weeks of study participation, the neurological outcome, the rate of reoperation, the time to reoperation, drug safety and compatibility, and participant quality of life (QOL).

Study Overview

• Status: Not yet recruiting
• Conditions: Chronic Subdural Hematoma
• Intervention / Treatment: Drug: Tranexamic Acid 500 MG; Drug: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Michael D Cusimano, MD, PhD; Phone Number: (+1)416-864-5312; Email: injuryprevention@smh.ca
• Study Contact Backup: Name: Abdelhakim Khellaf, MD; Phone Number: (+1)514-961-1953; Email: abdelhakim.khellaf@mail.utoronto.ca

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5B1T8
      • St. Michael's Hospital

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:

• Diagnosis of chronic subdural hematoma (CSDH)
• Written informed consent (patient, power of attorney or substitute decision maker)
• Competence to take study medication properly and regularly or access to caregiver 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 GFR ≤ 30 mL/min
• Hematuria, caused by diseases of renal parenchyma
• Concomitant intake of hormonal contraceptives, factor IX complex concentrates, and anti-inhibitor coagulant concentrates (factor VII, activated factor IX)
• History of angioplasty with cardiac stent placement, or cardiac (including mechanical) valve placement
• Active history of stroke (hemorrhagic and ischemic), or subarachnoid hemorrhage, within the past 6 months
• Consumption coagulopathy/disseminated intravascular coagulation (DIC) in the last 7 days
• History of malignant brain tumors (glioma, metastasis and others) or seizures within the 6 months
• Contraindication to stopping full therapeutic doses of non-ASA antiplatelets, warfarin, rivaroxaban, apixaban, dabigatran, or other anticoagulant for 2 weeks after surgery
• Inability of oral drug intake or missing support to guarantee oral drug intake
• SDH as caused by intracranial hypotension resulting from CSF shunt placement

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tranexamic Acid Arm; Participants in the experimental arm will receive tranexamic acid (TXA) during surgery for CSDH evacuation with a single 1000mg intraoperative intravenous (IV) dose. Participants with a body weight 60-100kg will also receive a post-operative dose regimen of 500 mg TXA orally, 3 times a day (TID). Weight deviations from this body weight range will be considered with a dose adjustment of 1000mg TXA two times a day (BID) for a body weight >100 kg, and 500 mg TXA BID for body weight <60kg.	Drug: Tranexamic Acid 500 MG; Tranexamic Acid 500mg oral tablets
Placebo Comparator: Placebo Control Arm; Participants in the control arm will placebo according to the same administration regimen.	Drug: Placebo; The placebo will consist of an identical capsule to over-encapsulated tranexamic acid oral tablet entirely filled with microcrystalline cellulose, and sealed.

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 CT-scan-based volume measurements comparing hematoma on CT scan performed at 4-8 weeks to hematoma on immediate post-operative CT scan.	At 4-8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Chronic subdural hematoma volume change	Change in hematoma volume in mL according to CT-scan-based volume measurements comparing hematoma on CT scan performed at 4-8 weeks to hematoma on immediate post-operative CT scan.	At 12 weeks
Rate of adverse events (AEs)	Adverse events investigated include: suspected stroke; myocardial infarction; deep vein thrombosis; thromboembolic events; decline in renal function; new-onset neurological deterioration Serious adverse events include: evidence of stroke; myocardial infarction; deep vein thrombosis; thromboembolic events; convulsions; severe allergic reactions; evidence of retinal degeneration; necessity of hospital admission; mortality	At 4, 8, and 12 weeks
36-Item Short Form Survey (SF-36)	Questionnaire assessing patient quality of life outcome profile	At 4, 8, 12 weeks
National Institutes of Health Stroke Scale (NIHSS)	Change in National Institutes of Health Stroke Scale (NIHSS) score (neurological outcome) at 4-8 weeks and 8-12 weeks, compared to the baseline visit score Minimum scale score: 0; Maximum scale score: 42. Higher score means worse neurological impairment.	At 4, 8, and 12 weeks
Modified Rankin Scale (mRS)	Change in Modified Rankin Scale (mRS) score (neurological outcome) at 4-8 weeks and 8-12 weeks, compared to the baseline visit score Minimum scale score: 0 (no symptoms); Maximum scale score: 6 (death). Higher score means worse neurological outcome.	At 4, 8, and 12 weeks
Markwalder's grading scale (MGS)	Change in Markwalder's grading scale (MGS) score (neurological outcome) at 4-8 weeks and 8-12 weeks, compared to the baseline visit score Minimum scale score: 0 (normal); Maximum scale score: 4. Higher score means worse neurological outcome.	At 4, 8, and 12 weeks
Rate of re-operation	Rate of re-operation during study course due to hematoma enlargement or other significant cause	At 4, 8, and 12 weeks
Time to reoperation	Time to reoperation during study course due to hematoma enlargement or other significant cause	At 4, 8, and 12 weeks

Collaborators and Investigators

• Sponsor: Unity Health Toronto
• Collaborators: The Physicians' Services Incorporated Foundation
• Investigators: Principal Investigator: Michael D Cusimano, MD, PhD, St. Michael's Hospital / University of Toronto

Study record dates

Study Major Dates

• Study Start (Anticipated): July 1, 2021
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: May 12, 2021
• First Submitted That Met QC Criteria: May 18, 2021
• First Posted (Actual): May 24, 2021

Study Record Updates

• Last Update Posted (Actual): May 24, 2021
• Last Update Submitted That Met QC Criteria: May 18, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Neurosurgery; Tranexamic acid; Chronic Subdural Hematoma
• 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: 17-232

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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