Tranexamic Acid to Prevent OpeRation in Chronic Subdural Hematoma. A Double-blind, Placebo-controlled, Multicentre, Randomized Controlled Clinical Trial
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 554
- 试验地点
- 1
- 主要终点
- surgery for cSDH
研究概览
简要总结
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.
详细描述
- INTRODUCTION AND RATIONALE Chronic subdural hematoma (cSDH) is a frequently occurring neurological disease of the elderly and common in daily neurosurgical practice. It consists of an extracerebral encapsulated collection of mostly liquefied old hematoma, located between the dura and arachnoid. The original small, and often asymptomatic, haemorrhage is caused by rupture of a bridging vein after, often minor, head trauma. Due to generalized cerebral atrophy, increased venous fragility, and the more frequent use of anticoagulation therapy, older people are more at risk of developing a cSDH.
During several weeks, the original hematoma is encapsulated by a membrane consisting of weak neocapillaries from where recurrent small bleedings occur. The pathophysiological mechanism is thought to be a problem in the local haemostasis due to fibrin degradation products of the original small hematoma that inhibit further haemostasis in the subdural space. Together with an osmotic draw of water, owing to its high protein content, this results in growth of the hematoma. Therefore, it usually takes several weeks for the cSDH to grow and become symptomatic.
Signs and symptoms arise due to compression of brain tissue. These can be generalised, such as headaches, light-headedness, cognitive disturbances, apathy, somnolence, seizures, frequent falling and depression. Also focal deficits, such as dysphasia, motor weakness or sensory disturbances, can be symptoms of a cSDH.
The current incidence of cSDH is estimated to be 15/100,000 per year. The number of patients with cSDH is expected to increase considerably in the near future due to the continuing growth of the elderly population, and the increase in the use of anticoagulation and anti-aggregation therapy. By 2030, the incidence is expected to rise up to 20/100,000 per year, thus making cSDH the most common neurosurgical condition in adults. In The Netherlands, this comes down to 3,600 new patients each year.
Treatment Treatment options are conservative and surgical. Conservative treatment currently consists of a wait-and-scan policy in which the patient is regularly monitored for neurological deterioration and growth of the hematoma on follow-up imaging. Anticoagulation and antiplatelet therapy is discontinued in low-risk patients, based on individual risk-benefit assessment and the discretion of the treating physician. If the clinical condition of the patient worsens, the indication for surgical evacuation of the hematoma is re-evaluated.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
double-blind
入排标准
- 年龄范围
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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).
排除标准
- •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;
研究组 & 干预措施
Tranexamic Acid
Tranexamic acid 500mg two times a day orally for a total of 28 days
干预措施: Tranexamic Acid 500Mg Tablet (Drug)
PLACEBO
Placebo capsules two times a day orally for a total of 28 days
干预措施: Placebo oral capsule (Drug)
结局指标
主要结局
surgery for cSDH
时间窗: within 12 weeks after start of treatment
number of patients who need to undergo surgery for cSDH
次要结局
- falling incidents(during the 12 week study period)
- cSDH volume(at four, eight and 12 weeks)
- neurological impairment(at four, eight and 12 weeks)
- patient health status 1(at 12 weeks)
- mortality rate(at 12 weeks)
- use of care(during the 12 week study period)
- performance in activities of daily living 2(at 12 weeks)
- health-related costs(during the 12 week study period)
- patient health status 2(at 12 weeks)
- cognitive functioning(at four, eight and 12 weeks)
- performance in activities of daily living 1(at 12 weeks)
- functional outcome(at 12 weeks)
研究者
Prof. dr. W.Peter Vandertop
chair Neurosurgery
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)