The Use of Tranexamic Acid in the Treatment of Symptomatic Subdural Hematoma

Официальное название

TRACE STUDY: A Randomized Controlled Trial Using Tranexamic Acid in the Treatment of Subdural Hematoma

Обзор

Subdural hematoma (SDH) is a common condition experienced after head injury. Blood collects on the surface of the brain, causing headaches which can progress to confusion, weakness, or even coma. While patients with SDH often receive surgery, not all patients require surgery right away to ease pressure on the brain. After surgery, there can be up to 30 percent chance of more bleeding and the need for more surgeries. Given this, a drug capable of lowering the chance of more bleeding and speeding the recovery of the patient is highly desirable. In this study, we will test a commonly used, cheap drug called Tranexamic Acid (TXA). While the body stops unwanted and sometimes dangerous bleeding naturally by forming blood clots, TXA stops these blood clots from breaking down, which helps to keep bleeding spots plugged. Our previous study showed that TXA helped speed up patients' recovery; but a larger number of patients is necessary to evaluate how well TXA works to reduce bleeding and improve patient-reported outcomes. In this study, regardless of the need for surgery, half of the patients will be randomly assigned to take TXA, while the other half will take a placebo, which is a look-alike substance that contains no active drug. We will measure multiple outcomes over time to determine if TXA is working and lowers healthcare and personal costs, while also taking blood and surgical samples, to better understand how this drug works in SDH patients.

Вмешательства

• Препарат Tranexamic acid (TXA)
  Marcan-Tranexamic Acid 500 mg oral tablet over-encapsulated to match the placebo. Sandoz-Tranexamic Acid 100 mg/mL solution for injection via intravenous (IV) added to a 100mL infusion bag of NaCl 0.9% and infused by slow intravenous injection over 20 minutes.
• Препарат Placebo
  Placebo 500 mg consisting of an identical capsule to over-encapsulated tranexamic acid oral tablet entirely filled with microcrystalline cellulose, and sealed. Placebo 100 mg/mL solution for injection via intravenous (IV) consisting of 0.9% sodium chloride (saline).

Первичные конечные точки

• European Quality of Life 5 Dimensions 5 Level Version (EQ-5D-5L) [Срок оценки: Every 2 weeks after randomization up to 45±10 days.]

Вторичные конечные точки (12)

• Patient-Reported Outcomes Measurement Information System (PROMIS) Scale v1.2 - Global Health. English and French versions [Срок оценки: Baseline and every 2 weeks after randomization up to 45±10 days, and then at 60-90 days, and 180±10 days after randomization.]
• PROMIS Item Bank v2.0 - Cognitive Function. English version [Срок оценки: Baseline and every 2 weeks after randomization up to 45±10 days, and then at 60-90 days, and 180±10 days after randomization.]
• PROMIS Item Bank v2.0 - Physical Function. English version [Срок оценки: Baseline and every 2 weeks after randomization up to 45±10 days, and then at 60-90 days, and 180±10 days after randomization.]
• PROMIS Item Bank v2.0 - Ability to Participate in Social Roles and Activities. English version [Срок оценки: Baseline and every 2 weeks after randomization up to 45±10 days, and then at 60-90 days, and 180±10 days after randomization.]
• Subdural hematoma volume change [Срок оценки: Baseline, 45±10 days after randomization, and 60-90 days if deemed necessary for the patient's routine care.]
• Number of subdural hematoma-related surgical interventions [Срок оценки: First admission, subsequent admissions up to 180 days after randomization]
• Recurrence rate of SDH [Срок оценки: 45±10 days, 60-90 days, and 180±10 days after randomization]
• Mortality [Срок оценки: During the course of study up to 180±10 days after randomization]
• Modified Rankin Scale [Срок оценки: Baseline, 45±10 days, 60-90 days, and 180±10 days after randomization]
• Disability Rating Scale [Срок оценки: Baseline, 45±10 days, 60-90 days, and 180±10 days after randomization]
• Montreal Cognitive Assessment [Срок оценки: Baseline, 45±10 days, and 60-90 days after randomization]
• Medical Consumption Questionnaire [Срок оценки: Baseline, 45±10 days, and 180±10 days after randomization]

Критерии участия

Критерии включения

• Patients aged 45 and older weighing between 45-150 kg diagnosed with symptomatic SDH will be included. SDH is defined as unilateral or bilateral crescentic collection of blood (hyper, iso, or hypodense, or mixed density) of greater than or equals to 8 mm in thickness along the cerebral convexity on CT of the head. Symptomatic SDH patients eligible for inclusion are those with SDH with one or more of the following symptoms attributable to the SDH: headache, gait disturbance, confusion or cognitive decline, limb weakness or numbness/paresthesia, speech or visual disturbance, drowsiness or impaired consciousness, seizures, impaired cognition, or memory loss at the time of assessment.

Критерии исключения

\- Patients will be excluded for any of the following conditions:

• Asymptomatic for longer than 72 hours
• SDH less than 8 mm in maximal thickness
• Have an acutely deteriorating neurological status (e.g., brain herniation with pupillary dilation, aneurysm rupture, etc.) that is likely to be fatal within 6 hours or less due to a predominantly acute SDH
• Presence of brain contusion larger than 5 cubic centimeters or subarachnoid hemorrhage (SAH) thicker than 10 mm with Glasgow Coma Scale (GCS)< 13
• Patients with primarily interhemispheric or tentorial SDH
• Hypersensitivity to TXA or any of the placebo ingredients
• Pregnancy
• Irregular menstrual bleeding with unidentified cause
• Known acquired colour vision disturbances
• Hematuria caused by renal parenchymal disease
• Acute and chronic renal insufficiency indicated by estimated Glomerular Filtration Rate (eGFR) ≤ 30 mL/min
• Concomitant intake of birth control pill and/or hormonal replacement therapy, and anti-inhibitor coagulant concentrates (factor VIII inhibitor bypass activity (FEIBA), factor VII, activated factor IX)
• Consumption coagulopathy/disseminated intravascular coagulation (DIC) in the last 7 days
• Not competent to take study medication properly and regularly or not having access to caregiver that is able to comply with study medication administration
• Mechanical heart valve
• Liver cirrhosis
• Recent venous and/or arterial thromboembolism within 6 months of study enrolment
• SDH caused by intracranial hypotension
• Known thrombophilia (e.g., antiphospholipid syndrome)
• Any active malignancy: metastatic cancer systemically or to the brain or a primary malignant brain tumour treated within the last 6 months
• Previous enrolment in this trial for a prior episode
• Time interval >3 days from the time of clinical assessment to eligibility assessment
• Patients weighing <45 kg or >150 kg
• Patients received any amount of TXA upon admittance to hospital prior to enrolment

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Лечение

Центры проведения

Канада · 1 центр

• St. Michael's Hospital — Toronto

Публикации

• Fu TS, Jing R, McFaull SR, Cusimano MD. Recent trends in hospitalization and in-hospital mortality associated with traumatic brain injury in Canada: A nationwide, population-based study. J Trauma Acute Care Surg. 2015 Sep;79(3):449-54. doi: 10.1097/ta.0000000000000733. PMID 26535433
• Jiang R, Zhao S, Wang R, Feng H, Zhang J, Li X, Mao Y, Yuan X, Fei Z, Zhao Y, Yu X, Poon WS, Zhu X, Liu N, Kang D, Sun T, Jiao B, Liu X, Yu R, Zhang J, Gao G, Hao J, Su N, Yin G, Zhu X, Lu Y, Wei J, Hu J, Hu R, Li J, Wang D, Wei H, Tian Y, Lei P, Dong JF, Zhang J. Safety and Efficacy of Atorvastatin for Chronic Subdural Hematoma in Chinese Patients: A Randomized ClinicalTrial. JAMA Neurol. 2018 No PMID 30073290
• Kudo H, Kuwamura K, Izawa I, Sawa H, Tamaki N. Chronic subdural hematoma in elderly people: present status on Awaji Island and epidemiological prospect. Neurol Med Chir (Tokyo). 1992 Apr;32(4):207-9. doi: 10.2176/nmc.32.207. PMID 1378564
• Balser D, Farooq S, Mehmood T, Reyes M, Samadani U. Actual and projected incidence rates for chronic subdural hematomas in United States Veterans Administration and civilian populations. J Neurosurg. 2015 Nov;123(5):1209-15. doi: 10.3171/2014.9.JNS141550. Epub 2015 Mar 20. PMID 25794342
• Brennan PM, Kolias AG, Joannides AJ, Shapey J, Marcus HJ, Gregson BA, Grover PJ, Hutchinson PJ, Coulter IC; British Neurosurgical Trainee Research Collaborative. The management and outcome for patients with chronic subdural hematoma: a prospective, multicenter, observational cohort study in the United Kingdom. J Neurosurg. 2017 Mar 17:1-8. doi: 10.3171/2016.8.JNS16134.test. Online ahead of print. PMID 28306417
• Rauhala M, Helen P, Huhtala H, Heikkila P, Iverson GL, Niskakangas T, Ohman J, Luoto TM. Chronic subdural hematoma-incidence, complications, and financial impact. Acta Neurochir (Wien). 2020 Sep;162(9):2033-2043. doi: 10.1007/s00701-020-04398-3. Epub 2020 Jun 10. PMID 32524244
• Balser D, Rodgers SD, Johnson B, Shi C, Tabak E, Samadani U. Evolving management of symptomatic chronic subdural hematoma: experience of a single institution and review of the literature. Neurol Res. 2013 Apr;35(3):233-42. doi: 10.1179/1743132813Y.0000000166. PMID 23485050
• Lee KS. Natural history of chronic subdural haematoma. Brain Inj. 2004 Apr;18(4):351-8. doi: 10.1080/02699050310001645801. PMID 14742149

Идентификаторы

NCT: NCT05713630 · 471164

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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