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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cilostazol treatment with conventional treatment | Experimental | The drug treatment group will receive two consecutive weeks of Cilostazol two days after admission and receive conventional treatment as well. |
|
| Conventional treatment only | Placebo Comparator | The conventional treatment group will receive conventional internal medicine treatment. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Pletaal 100mg/tab | Drug | Two consecutive weeks of Cilostazol (50mg BID) two days after admission |
|
| Measure | Description | Time Frame |
|---|---|---|
| Hematoma size comparison at 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. | 16 days post-ICH |
| Measure | Description | Time Frame |
|---|---|---|
| Subject's National Institute of Health Stroke Scale (0-42) score change 16/30/90 days post-ICH | Subject's National Institute of Health Stroke Scale (0-42) score change 16/30/90 days post-ICH. Higher scores indicating greater severity. | 16/30/90 days post-ICH |
| Subject's mRankin Scale score(0-6) change 30/90 days post-ICH compared with pre-treatment status. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of patients that develop hematoma expansion | Safety outcome 1 | 90 days |
| Number of patient that require surgical evacuation of hematoma or open craniotomy for pressure relief | Safety outcome 2 |
Inclusion criteria:
Exclusion criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Hsin-Hsi Tsai, MD, PhD | Contact | +886-9-72652200 | tsaihsinhsi@gmail.com |
| Name | Affiliation | Role |
|---|---|---|
| Hsin-Hsi Tsai, MD, PhD | Department of Neurology, National Taiwan University Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| National Taiwan University Hospital | Recruiting | Taipei | Not Required For This Country | 100225 | Taiwan |
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| ID | Term |
|---|---|
| D002543 | Cerebral Hemorrhage |
| ID | Term |
|---|---|
| D020300 | Intracranial Hemorrhages |
| D002561 | Cerebrovascular Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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| Conventional internal medicine treatment | Procedure | Receives only conventional internal medicine treatment |
|
Subject's mRankin Scale score(0-6) change 30/90 days post-ICH compared with pre-treatment status. (the ratio of mRS score 0-1 and 0-2, with higher scores indicating greater severity.) |
| 30/90 days post-ICH |
| The difference of DCE-MRI time to maximal intensity between drug treatment group and conventional treatment group. | 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. | Hematoma resorption rate difference between drug treatment group and conventional treatment group 16 days post-ICH. | 16 days post-ICH |
| Within 16 days |
| Number of any adverse event or severe adverse event | Safety outcome 3 | Within 16 days |
| D009422 | Nervous System Diseases |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D006470 | Hemorrhage |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |