Clinical trial NCT06504576: Effect of Cilostazol in Promoting Hematoma Clearance After Intracerebral Hemorrhage
Official title: Effect of Cilostazol in Promoting Hematoma Clearance After Intracerebral Hemorrhage: A Phase-II Open Label Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: ICH - Intracerebral Hemorrhage
Lead sponsor: National Taiwan University Hospital
Sponsor class: OTHER
First posted: 2024-07-17
Enrollment: 100
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion criteria:

1. Adult patients (at least 20 years old, no upper limit)
2. ICH located in the thalamus or basal ganglia.
3. ICH score less than 3 (hematoma volume no greater than 15 ml) and was admitted within 24 hours since onset.
4. The patient or his/her legal representative agrees to join this trial and accept the arrangements of tests within this trial.

Exclusion criteria:

1. ICH in the cerebral lobar areas or under the cerebellar tentorium, or ICH score greater than 3.
2. Surgical intervention was suggested after evaluation
3. Subject has brain trauma, structural brain disease, metabolic brain disease, neuroinflammatory disease and brain tumor.
4. Subject that cannot accept image examination, including but not limited to unable to cooperate, disruption of image quality due to agitation, unstable hemodynamics, has MRI-incompatible pacemakers, has aneurysmal clip or claustrophobia.
5. Subject has contraindication for using contrast medium, including chronic kidney failure (CCr \< 30ml/min) or allergic to contrast medium.
6. Subject is currently pregnant or is scheduled to be pregnant within the following 6 months.
7. Subject is taking other antithrombotics, including antiplatelet drugs (Aspirin, Clopidogrel, Ticagrelor) and oral anticoagulative (Warfarin, Dabigatran, Rivaroxaban Apixaban, Edoxaban) when ICH happened.
8. Subject has contraindication to using Cilostazol, such as heart failure of any severity, coagulative disorders, ventricular tachycardia, ventricular fibrillation, multi-focal ventricular arrhythmia, severe tachycardic arrhythmia, unstable angina, myocardial infarction in recent 6 months, or had received coronary intervention.
9. Life expectancy less than 3 months.
10. Subject has known allergy to drugs used in the trial and was designated not suitable to enroll in this trial by the host.
11. Subject or his/her legal representative does not agree to join this trial.

Primary outcomes:
measure: Primary Outcome
timeFrame: 16 days post-ICH
Secondary outcomes:
measure: Secondary outcome 1
timeFrame: 16/30/90 days post-ICH
measure: Secondary outcome 2
timeFrame: 30/90 days post-ICH
measure: Secondary outcome 3
timeFrame: 16 days post-ICH
measure: Secondary outcome 4
timeFrame: 16 days post-ICH
Other outcomes:
measure: Safety outcome 1
timeFrame: 90 days
measure: Safety outcome 2
timeFrame: Within 16 days
measure: Safety outcome 3
timeFrame: Within 16 days
Locations:
Study officials:
affiliation: Department of Neurology, National Taiwan University Hospital
name: Hsin-Hsi Tsai, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: