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

Primary Purpose

Chronic Subdural Hematoma

Status
Not yet recruiting
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
Tranexamic Acid 500 MG
Placebo
Sponsored by
Unity Health Toronto
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Subdural Hematoma focused on measuring Tranexamic acid, Chronic Subdural Hematoma, Neurosurgery

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • St. Michael's Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Tranexamic Acid Arm

Placebo Control Arm

Arm Description

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.

Participants in the control arm will placebo according to the same administration regimen.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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
36-Item Short Form Survey (SF-36)
Questionnaire assessing patient quality of life outcome profile
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.
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.
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.
Rate of re-operation
Rate of re-operation during study course due to hematoma enlargement or other significant cause
Time to reoperation
Time to reoperation during study course due to hematoma enlargement or other significant cause

Full Information

First Posted
May 12, 2021
Last Updated
May 18, 2021
Sponsor
Unity Health Toronto
Collaborators
The Physicians' Services Incorporated Foundation
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1. Study Identification

Unique Protocol Identification Number
NCT04898712
Brief Title
Tranexamic Acid in the Treatment of Residual Chronic Subdural Hematoma -2
Acronym
TRACE-2
Official Title
Tranexamic Acid in the Treatment of Residual Chronic Subdural Hematoma: An Observer-blinded, Randomized Controlled Trial
Study Type
Interventional

2. Study Status

Record Verification Date
May 2021
Overall Recruitment Status
Not yet recruiting
Study Start Date
July 2021 (Anticipated)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
December 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Unity Health Toronto
Collaborators
The Physicians' Services Incorporated Foundation

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Subdural Hematoma
Keywords
Tranexamic acid, Chronic Subdural Hematoma, Neurosurgery

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Masking Description
Double-blind
Allocation
Randomized
Enrollment
90 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Tranexamic Acid Arm
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo Control Arm
Arm Type
Placebo Comparator
Arm Description
Participants in the control arm will placebo according to the same administration regimen.
Intervention Type
Drug
Intervention Name(s)
Tranexamic Acid 500 MG
Intervention Description
Tranexamic Acid 500mg oral tablets
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
The placebo will consist of an identical capsule to over-encapsulated tranexamic acid oral tablet entirely filled with microcrystalline cellulose, and sealed.
Primary Outcome Measure Information:
Title
Chronic subdural hematoma volume change
Description
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.
Time Frame
At 4-8 weeks
Secondary Outcome Measure Information:
Title
Chronic subdural hematoma volume change
Description
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.
Time Frame
At 12 weeks
Title
Rate of adverse events (AEs)
Description
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
Time Frame
At 4, 8, and 12 weeks
Title
36-Item Short Form Survey (SF-36)
Description
Questionnaire assessing patient quality of life outcome profile
Time Frame
At 4, 8, 12 weeks
Title
National Institutes of Health Stroke Scale (NIHSS)
Description
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.
Time Frame
At 4, 8, and 12 weeks
Title
Modified Rankin Scale (mRS)
Description
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.
Time Frame
At 4, 8, and 12 weeks
Title
Markwalder's grading scale (MGS)
Description
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.
Time Frame
At 4, 8, and 12 weeks
Title
Rate of re-operation
Description
Rate of re-operation during study course due to hematoma enlargement or other significant cause
Time Frame
At 4, 8, and 12 weeks
Title
Time to reoperation
Description
Time to reoperation during study course due to hematoma enlargement or other significant cause
Time Frame
At 4, 8, and 12 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Michael D Cusimano, MD, PhD
Phone
(+1)416-864-5312
Email
injuryprevention@smh.ca
First Name & Middle Initial & Last Name or Official Title & Degree
Abdelhakim Khellaf, MD
Phone
(+1)514-961-1953
Email
abdelhakim.khellaf@mail.utoronto.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael D Cusimano, MD, PhD
Organizational Affiliation
St. Michael's Hospital / University of Toronto
Official's Role
Principal Investigator
Facility Information:
Facility Name
St. Michael's Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5B1T8
Country
Canada

12. IPD Sharing Statement

Plan to Share IPD
No

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

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