Tranexamic Acid to Prevent OpeRation in Chronic Subdural Hematoma. A Double-blind, Placebo-controlled, Multicentre, Randomized Controlled Clinical Trial

NL63794.018.18

Rationale: Chronic subdural hematoma (cSDH) is a frequently occurring disease, occurring mainly in the elderly. Surgical evacuation is effective, but also associated with life-threatening risks. In these old, often frail, patients with multi-comorbidity, surgery also comes with significant risks for future cognitive functioning and therefore, loss of independency. In five small retrospective series, tranexamic acid (TXA), an antifibrinolytic drug, showed a beneficial effect on the spontaneous resolution of the hematoma and, with that, the necessity for surgery. This randomised, placebo-controlled clinical trial aims to prove the efficacy of TXA. Objectives: Primarily to evaluate the efficacy of TXA to prevent surgery for cSDH. Secondarily to evaluate the efficacy of TXA to reduce cSDH volume, neurological impairment (mNIHSS), the incidence of falling incidents, the mortality rate, the use of care and health-related costs (iMCQ and iPCQ), to improve cognitive functioning (MOCA), performance in activities of daily living (Barthel and Lawton-Brody), functional outcome (mRS), the level of quality of life. Study design: Double-blind placebo-controlled multicentre randomized clinical trial. Study population: All patients, age 50 and above, diagnosed with cSDH for whom a conservative treatment is selected as primary treatment strategy. Intervention: The intervention group will receive oral TXA 500mg twice daily for 4 weeks, the control group will receive a placebo twice daily. The TXA or placebo treatment is additional to standard care. Main study endpoint: The number of patients requiring surgery within 12 weeks after start treatment. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Patients will use the study medication twice daily for four weeks. Follow-up is at 4, 8and 12 weeks with a standard CT-scan of the head, outpatient clinic visits and 4 patient-reported questionnaires. These outpatient clinic visits are standard care; the third CT-scan, the questionnaires and extra clinical tests are extra. Each patient may benefit from the study if the study medication proves effective in preventing surgery for cSDH, whereas the risk of potential side effects of the medication is slight (e.g. the risk of thromboembolic events is only 0.01-0.1%). Surgery remains a possibility for those patients in whom study medication is not effective.

2018-06-19

2023-12-31

2024-04-30

Recruiting

Early phase I

140

Inclusion Criteria: * On CT confirmed cSDH * Primary conservative treatment, based on clinical symptoms: Glasgow Coma Scale score \>=14, mNIHSS score \<=4 and a stable neurological deficit (no new, or progression of, symptoms between the assessment by the neurologist and the assessment by the neurosurgeon). Exclusion Criteria: Primary surgical treatment based on one or more of the following symptoms or parameters: medically intractable headache, midline shift \>10mm, imminent death within 24 hours; * Structural causes for subdural haemorrhage, e.g. arachnoid cysts, cortical vascular malformations and a history of cranial surgery \<1year; * Aneurysmal subarachnoid haemorrhage; * Active treatment for deep vein thrombosis, pulmonary embolism or cerebral thrombosis (secondary prophylaxis is not considered to be active treatment); * Active intravascular clotting or disseminated intravascular coagulation; * Known hypersensitivity or allergy to TXA or to any of the ingredients; * History of a blood coagulation disorder (hypercoagulability disorder); * History of severe impairment of renal function (eGFR \<30ml/min or serum creatinine \>150μmol/L); * History of anaemia (haemoglobin \<6mmol/L); * History of convulsions; * History of inability to safely swallow oral medication. * Inability to obtain informed consent from the patient or legal representative (when the patient has a depressed level of consciousness as described in paragraph 11.2), including language barrier;

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2023-07-24