Aneurysmal Subarachnoid Hemorrhage
Conditions
Keywords
Aneurysmal Subarachnoid Hemorrhage, Cilostazol, Delayed Cerebral Ischemia
Brief summary
The investigators propose to conduct a multicenter randomized trial to test whether cilostazol reduces the incidence of delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH) and improves patients' neurological prognosis, while assessing its safety.
Detailed description
The investigators propose to conduct a multicenter randomized trial to test the primary hypothesis of whether cilostazol reduces the incidence of delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH) and improves patients' neurological prognosis, while assessing its safety. The investigators will recruit 316 patients from 30 hospitals in China. Eligibility criteria for the trial participants include Aged 18-80 years. Diagnosed with subarachnoid hemorrhage (SAH) by computed tomography (CT) scan, and the responsible aneurysm is identified by computed tomography angiography (CTA) or digital subtraction angiography (DSA). Received aneurysm coil embolization or craniotomy clipping within 72 hours of symptom onset. Hunt-Hess grade II-IV. No rebleeding or new intracranial hemorrhage is shown on head CT within 6 hours after surgery. Understand and follow the procedures of clinical trial, participate voluntarily and sign the informed consent (the informed consent can be signed voluntarily by the person or guardian). Patients with multiple aneurysms, Modified Rankin Scale (mRS) score ≥ 3 before onset, contraindications to cilostazol use, severe organic diseases and an expected survival time of less than 90 days, severe liver insufficiency or renal insufficiency before randomization, aneurysm treatment requiring the use of other antiplatelet drugs after interventional therapy, receiving treatment with other investigational drugs or device trials currently will be excluded. Patients will be randomly assigned to the experimental group or control group at a 1:1 ratio. Experimental Group patients will receive cilostazol 100 mg twice daily for 14 consecutive days, in addition to the standard aSAH treatment. Control Group patients will receive a placebo twice daily (bid) for 14 consecutive days, in addition to the standard aSAH treatment. The primary study endpoint is incidence of delayed cerebral ischemia (DCI) in patients with aneurysmal subarachnoid hemorrhage (aSAH) within 14±2 days after randomization. Other secondary endpoints include neurological function prognosis at 90±7 days after randomization, incidence of intracranial rebleeding events within 90±7 days after randomization, incidence of other severe bleeding events within 90±7 days after randomization. This trial will provide important information for the development of clinical guidelines for reducing delayed cerebral ischemia (DCI) in patients with aneurysmal subarachnoid hemorrhage (aSAH).
Interventions
Within 24 hours after randomization, patients will receive cilostazol 100 mg twice daily (BID) for 14 consecutive days, in addition to the standard aSAH treatment.
DRUGplacebo
Within 24 hours after randomization, patients will receive a placebo twice daily (BID) for 14 consecutive days, in addition to the standard aSAH treatment.
Sponsors
Beijing Tiantan Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Patients will be randomly assigned to the following treatment groups at a 1:1 ratio: Experimental Group： Within 24 hours after randomization, patients will receive cilostazol 100 mg twice daily for 14 consecutive days, in addition to the standard aSAH treatment. Control Group： Within 24 hours after randomization, patients will receive a placebo twice daily (bid) for 14 consecutive days, in addition to the standard aSAH treatment.
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Aged 18-80 years. * Diagnosed with subarachnoid hemorrhage (SAH) by computed tomography (CT) scan, and the responsible aneurysm is clearly identified by computed tomography angiography (CTA) or digital subtraction angiography (DSA). * Received aneurysm coil embolization or craniotomy clipping within 72 hours of symptom onset. * Hunt-Hess grade II-IV. * No rebleeding or new intracranial hemorrhage is shown on head CT within 6 hours after surgery. * Understand and follow the procedures of clinical trial, participate voluntarily and sign the informed consent (the informed consent can be signed voluntarily by the person or guardian)
Exclusion criteria
* Multiple aneurysms (\>1aneurysms confirmed by CTA/DSA) * Modified Rankin Scale (mRS) score ≥ 3 before onset * Patients with contraindications to cilostazol use: 1. Allergy to cilostazol 2. Severe heart failure（New York Heart Association (NYHA) Functional Classification Grade III or IV） 3. Coagulation disorders or systemic bleeding (e.g., hemophilia, gastrointestinal bleeding, hemoptysis, etc.) 4. Pregnant or lactating women * Patients with severe organic diseases and an expected survival time of less than 90 days * Severe liver insufficiency or renal insufficiency before randomization * Aneurysm treatment requiring the use of other antiplatelet drugs after interventional therapy * Currently receiving treatment with other investigational drugs or device trials
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of delayed cerebral ischemia (DCI) | At 14±2 days after randomization | Delayed cerebral ischemia (DCI) was defined as the occurrence of clinical deterioration, including new-onset focal neurological deficits (e.g., hemiplegia, aphasia, apraxia, hemianopia, or neglect) and/or a decrease in the consciousness (a Glasgow Coma Scale \[GCS\] score reduction of at least 2 points, either in the total score or any individual subscore), with symptoms lasting for at least 1 hour and not occurring immediately after aneurysm surgery. Other potential causes of clinical deterioration (e.g., hydrocephalus, rebleeding, fever, infection, metabolic disturbance, epilepsy, etc.) were excluded. Alternatively, DCI was defined as the presence of new infarct lesions on follow-up brain CT/MRI that were not detected on the initial admission brain CT or post-operative follow-up brain CT. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Neurological function prognosis | At 90 days after randomization | The modified Rankin Scale (mRS) score and Glasgow Outcome Scale (GOS) score were evaluated at 90 days after randomization. Favorable outcome was defined as an mRS score of 0-3 (0-3 indicating no disability to moderate disability; 4-6 indicating moderately severe disability to death) and a GOS score of 3-5 (3-5 indicating severe disability to good recovery). |
| Incidence of intracranial rebleeding events | At 90±7 days after randomization | Any new intracranial hemorrhage occurring within 90 days after randomization (whether rebleeding in the surgical area or new intracranial hemorrhage events following cilostazol administration), confirmed by comparing non-contrast CT scan results during follow-up with those of the last post-operative non-contrast CT scan before randomization. |
| Incidence of other severe bleeding events | At 90 days after randomization | Any new symptomatic intracranial hemorrhage or any new moderate or severe hemorrhage occurring within 90 days after randomization (defined according to the Bleeding Academic Research Consortium \[BARC\] criteria as hemorrhage requiring endoscopic treatment, surgical intervention, or blood transfusion \[Types 2-3\] and fatal hemorrhage \[Type 5\]). |
Countries
China
Contacts
Primary ContactLiping Liu
Outcome results
None listed