Tranexamic Acid Therapy For The Treatment of Subdural Hematomas

Обзор

This Phase II randomized, placebo-controlled, double-blinded trial is the first step in our endeavor to improve the clinical outcomes of patients with chronic subdural hematomas (cSDH). Patients who are deemed to not need surgery for their cSDH will be randomly assigned to either the treatment group or the placebo group. Both groups will take a 650mg tablet once daily for 21 weeks and follow the standard of care monitoring for cSDH which is neurological testing and imaging at 6 weeks, 12 weeks, and 21 weeks. With this study, we hope to establish the safety and efficacy of using TXA PO to resolve cSDH without the need for surgical intervention.

Подробное описание

Patients must first be evaluated by a neurosurgeon and concluded to be managed conservatively, without a surgical procedure. Then patients may be enrolled into the study if they meet the specific inclusion and exclusion criteria mentioned above.

If the patient signs the informed consent and is enrolled into the study, the treating physician will inform the study team. The patient will be randomized into either treatment or placebo group per the above algorithm. The study will be double-blind, and only the statistician will know the patient groupings.

In the event that unblinding is needed, the statistician will inform the treating physician of the patient's study group.

Tranexamic acid (TXA), the study agent, or matching placebo will be prescribed as a 650mg tablet to be taken once daily for 21 weeks. The drug will be provided as an oral tablet from the pharmacy. The placebo will be a similar tablet. Once prescribed patients will follow the standard of care for conservative management of chronic subdural hematoma.

Baseline evaluation

After obtaining informed consent and prescription of study agent a baseline clinical examination will be done to assess patient's neurological status, including National Institute of Health Stroke Scale (NIHSS), Modified Rankin Score (mRS), and Glasgow Outcome Scale-Extended (GOSE) scales as well as record initial CT scans.

Week 6 follow-up

At the week 6 follow-up, patients will receive a head CT scan to evaluate for changes in hematoma volume and evaluate for coagulopathies. Functional outcomes will also be assessed, including NIHSS, mRS, and GOSE scales.

Week 12 follow-up

At the week 12 follow-up, patients will receive a head CT scan to evaluate for changes in hematoma volume, evaluate for coagulopathies, and hematoma recurrence. Functional outcomes will also be assessed, including NIHSS, mRS, and GOSE scales.

Week 21 follow-up

At the final week 21 follow-up, patients will receive a head CT scan to evaluate for changes in hematoma volume and recurrence. Functional outcomes will also be assessed, including NIHSS, mRS, and GOSE scales.

Standard of care consists of closely monitoring for new neurological symptoms, including altered mental status, focal neurological deficit, headache, or seizures, during hospital admission and during follow-up visits. If new neurological symptoms arise or if existing neurological symptoms do not improve based on progressive or non-resolving hematoma, surgical treatment may be reconsidered. The head CT is part of the standard of care for patients with subdural hematomas. The addition of the study agent, TXA or placebo, is the investigational part of the protocol and not standard of care. Scans will be copied for blinded independent radiologic review, and functional outcomes will be performed by the study physicians.

Вмешательства

• Препарат Tranexamic Acid 650 MG
  PO administration of TXA tablet
• Препарат Placebo
  PO administration of placebo tablet

Первичные конечные точки

• Rate of resolution measured as the cSDH volume or diameter [Срок оценки: 6 weeks, 12 weeks, 21 weeks]

Вторичные конечные точки (7)

• cSDH volume (measured as volume or diameter on follow-up CT scan of the head) [Срок оценки: 6 weeks, 12 weeks, 21 weeks]
• Proportion of patients needing surgery [Срок оценки: 12 weeks, 12 weeks, 21 weeks]
• Hematoma recurrence Hematoma recurrence [Срок оценки: 12 weeks, 12 weeks, 21 weeks]
• Neurological outcome assessed by NIHSS [Срок оценки: 6 weeks, 12 weeks, 21 weeks]
• Functional outcome assessed by mRS [Срок оценки: 6 weeks, 12 weeks, 21 weeks]
• Functional outcome assessed by GOSE [Срок оценки: 6 weeks, 12 weeks, 21 weeks]
• Occurrence of adverse events [Срок оценки: 6 weeks, 12 weeks, 21 weeks]

Критерии участия

Критерии включения

• CT scan demonstrating existence of a subdural hematoma, unilateral or bilateral, containing a chronic component
• Neurosurgeon evaluation deemed patient to not need surgery
• Diagnosis within the last 14 days
• Signed informed consent
• Competence to take study medications properly and regularly or access to care giver that is able to comply with accurate study medication administration

Критерии исключения

• Planned surgery, burr-hole craniostomy or mini-craniotomy for their chronic subdural hematoma based on one or more of the following symptoms: medically intractable headache, midline shift >5mm, SDH thickness >10mm, increased ICP, imminent death within 24 hours
• Structural causes for subdural hemorrhage (arachnoid cysts, cortical vascular malformations)
• Recent ischemic stroke
• Other concomitant intracranial pathology (intracranial malignancy)
• Active malignancy
• Need for chronic therapeutic anticoagulation (i.e. atrial fibrillation)
• Acute subdural hematoma with no chronic component
• Active treatment for deep vein thrombosis, pulmonary embolism or cerebral thrombosis (secondary prophylaxis is not considered to be active treatment)
• Known hereditary thrombophilia, including Factor V Leiden, Antithrombin III mutation, Protein C deficiency, Protein S deficiency
• History of thrombosis or thromboembolism, including retinal vein or artery occlusions
• An intrinsic risk of thrombosis or thromboembolism
• Aneurysmal subarachnoid hemorrhage
• Concurrent use of Factor IX complex concentrate or anti-inhibitor coagulant concentrates
• Concurrent use of all-trans retinoic acid
• Active intravascular clotting or disseminated intravascular coagulation
• Need for tissue plasminogen activators
• Known hypersenstivity to TXA or any of the ingredients
• Acute and chronic renal insufficiency indicated by glomerular filtration rate (GFR) < 60 mL/min or creatinine > 2.8 mg/dL
• Hematuria, caused by diseases of renal parenchyma
• Pregnancy or breastfeeding\*
• Concomitant hormonal contraception\*
• History of convulsions
• History of angioplasty with cardiac stent placement or mechanical heart valve
• Any concern from the attending physician

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

Четверное слепое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT06718751 · H-55608

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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