Effect of Cilostazol in Promoting Hematoma Clearance After Intracerebral Hemorrhage: A Phase-II Open Label Study
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Hematoma size comparison at 16 days post-ICH
研究概览
简要总结
Intracerebral hemorrhage (ICH) is a dangerous form of stroke with high mortality rate. Other than evacuating the hematoma with surgical procedures, there is no current effective internal medicine treatment. Currently, there are many novel internal medicine treatment under development, one of which is the promotion of endogenous hematoma clearance. Our team recently found out that the meningeal lymphatic system plays an important role in clearing hematoma post-ICH, meaning that promoting the drainage function of the meningeal lymphatic system may have a certain level of help for improving the prognosis of ICH.
Cilostazol is an anti-PDE3 type antiplatelet agent with the function of preventing peripheral arterial occlusion disease and stroke. Cilostazol has been proven to promote lymphatic endothelial cell proliferation and the drainage function of the lymphatic system. Our animal research points out that Cilostazol speeds up hematoma clearance post-ICH and generates neuroprotective effects, thereby improving prognosis and providing a new internal medicine treatment for ICH.
Due to the fact that there is no clinical trial looking into the hematoma resorption effect of Cilostazol in ICH patients, this trials aims to understand the safety and hematoma resorption efficacy of Cilostazol in acute ICH patients. Investigators estimate to enroll 100 patients in National Taiwan University Hospital (NTUH) within 3 years. The patients would be randomized into two groups, one receiving Cilostazol (two weeks, 50mg BID) and conventional treatment, and the other group receiving only conventional treatment. Investigators will assess the patients' neurological outcome and functional aspects (NIHSS, modified Rankin Scale) two weeks / one month / three months after ICH. Investigators will also use MRI to measure hematoma size to evaluate hematoma resorption (primary endpoint and safety endpoint). MRI will also be used to measure the drainage effect of the meningeal lymphatics.
详细描述
After the subject is sent to the emergency department, he/she will receive a CT scan to evaluate the size and location of the hematoma. ICH score will be used to evaluate the severity of the subject. The subject will then be randomized to the drug treatment group or the conventional treatment group. The drug treatment group would receive two consecutive weeks of Cilostazol (50mg BID) two days after admission and conventional treatment, whereas the conventional treatment group only receives conventional internal medicine treatment. The subject would receive an MRI scan after finishing his/her course of Cilostazol (16 +/- 2 days post-ICH) to assess the size of the hematoma and brain meningeal lymphatic drainage effects. Investigators will gather information from the subject such as age, sex, vascular risk factors, past antithrombotic treatment history and past stroke history. Basic biochemistry panels (including coagulation function and complete blood count) and clinical data (including neurological deficits and blood pressure on admission) will also be gathered. Investigators are scheduled to perform the NIHSS scale and the modified Rankin Scale 1/14/30/90 days after ICH to evaluate the level of disability.
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
- None
入排标准
- 年龄范围
- 20 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult patients (at least 20 years old, up to 80 years old)
- •ICH located in the thalamus or basal ganglia.
- •ICH score less than 3 (hematoma volume not greater than 15 ml) and was admitted within 24 hours since onset.
- •The patient or his/her legal representative agrees to join this trial and accept the arrangements of tests within this trial.
- •Patients with normal bone marrow and hematopoiesis (Red blood cell count, white blood cell count, platelet count within reference value).
- •Patients with normal liver function (Aspartate aminotransferase (AST), Alanine aminotransferase (ALT) and Gamma-glutamyl transferase (γ-GT) within reference value)
- •Patients with normal renal function (Blood urea nitrogen (BUN), creatinine and estimated glomerular filtration rate (eGFR) within reference value)
- •Patients with normal coagulation function (Platelet count, prothrombin time (PT), activate partial thromboplastin time (aPTT), international normalized ratio (INR) within reference value)
排除标准
- •Image studies conducted after intracerebral incidence and before enrollment showing higher bleeding risks such as spot sign in computed tomography angiography, new intraventricular hemorrhage (IVH), IVH expansion, irregular hematoma border, heterogenous hematoma component or hematoma expansion.
- •Intracerebral hemorrhage located in the cerebral area, below the cerebellar tentorium or ICH score greater than 3 (not including 3).
- •Surgical intevention such as decompressive craniotomy or hematoma evacuation was suggested after evaluation by neurosurgeon.
- •Patients with history of brain trauma, structural brain disease, metabolic brain disease, neuroinflammatory disease or brain neoplasms.
- •Patients that cannot tolerate image studies, including but not limited to those that cannot cooperate, affecting image quality due to agitation, presenting with unstable hemodynamics, installed with pacemakers incompatible with magnetic resonance imaging (MRI), has brain aneurysm clips or clasutorphobic.
- •Patients with medical contraindications to MRI contrast medium, including chronic renal failure (Creatinine clearance rate less than 30ml/min).
- •Patients currently pregnant or expecting pregnancy or breastfeeding in six months.
- •Patients taking oral anti-platelet medication (aspirin, clopidogrel, ticagrelor, cilostzaol) or anti-coagulant (warfarin, dabigatran, rivaroxaban, apixaban, edoxaban) when ICH occurred.
- •Patients with medical contraindications to cilostazol, including heart failure with any severity, any coagulopathy, ventricular tachycardia, ventricular fibrillation, mulitfocal ventricular arrhythmia, severe tachycardic arrhythmia, unstable angina, myocardial infarction within six months, has history of receiving percutaneous coronary intervention, active pathological bleeding and severe hepatorenal insufficiency.
- •Patients with poor blood pressure control (defined as systolic blood pressure greater than 160 mmHg under anti-hypertensive medication).
- •Patients with unstable neurological conditions (defined as increase in National Institute of Health Stroke Scale (NIHSS) greater than 4 or newly occurred conscious change during admission).
- •Patients with life expectancy less than three months.
- •Patients with known allergy to any of the ingredient of the trial medication, and deemed unsuitable for enrollment of the study by the trial host.
- •Patient or legal guardian of the patient refuses to be enrolled within the study.
研究组 & 干预措施
Cilostazol treatment with conventional treatment
The drug treatment group will receive two consecutive weeks of Cilostazol two days after admission and receive conventional treatment as well.
干预措施: Pletaal 100mg/tab (Drug)
Cilostazol treatment with conventional treatment
The drug treatment group will receive two consecutive weeks of Cilostazol two days after admission and receive conventional treatment as well.
干预措施: Conventional internal medicine treatment (Procedure)
Conventional treatment only
The conventional treatment group will receive conventional internal medicine treatment.
干预措施: Conventional internal medicine treatment (Procedure)
结局指标
主要结局
Hematoma size comparison at 16 days post-ICH
时间窗: 16 days post-ICH
Hematoma size comparison at 16 days post-ICH in the drug treatment group and conventional treatment group by measuring MRI T2WI. Whether taking two consecutive weeks of Cilostazol causes hematoma expansion.
次要结局
- Subject's National Institute of Health Stroke Scale (0-42) score change 16/30/90 days post-ICH(16/30/90 days post-ICH)
- Subject's mRankin Scale score(0-6) change 30/90 days post-ICH compared with pre-treatment status.(30/90 days post-ICH)
- The difference of DCE-MRI time to maximal intensity between drug treatment group and conventional treatment group.(16 days post-ICH)
- Hematoma resorption rate difference between drug treatment group and conventional treatment group 16 days post-ICH.(16 days post-ICH)