Cilostazol and Nimodipine Combined Therapy After Aneurysmal Subarachnoid Hemorrhage (aSAH)

Study Overview
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Brief Summary
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The investigators seek to demonstrate that the combined use of cilostazol and nimodipine will significantly decrease the rate of delayed cerebral infarction and cerebral vasospasm after cerebrovascular intervention when compared to nimodipine alone.

Detailed Description
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This research study is for people who have a brain hemorrhage, due to a ruptured aneurysm. Adding the drug cilostazol to the standard care may improve outcomes after surgery. The blood within the brain following aneurysmal hemorrhage can have harmful effects on the blood vessels causing them to narrow and thus decrease blood flow; this process is called vasospasm. Decreased blood flow in the brain can lead to more damage. Delayed cerebral ischemia is a complication which is believed to be a consequence of reduced blood flow to the brain following this type of hemorrhage. Cilostazol opens blood vessels and reduces the formation of blood clots. The standard treatment of these hemorrhages currently involves the use of nimodipine which also relaxes blood vessels and allows blood to flow more freely. The combination of these two drugs cilostazol and nimodipine may improve neurologic outcomes after surgery.

Official Title
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Efficacy and Safety of Cilostazol-Nimodipine Combined Therapy on Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage (aSAH): A Prospective, Randomized, Double-Blinded, Placebo-Controlled Trial

Conditions
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Aneurysmal Subarachnoid Hemorrhage

Intervention / Treatment
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* Drug: Cilostazol 100 MG
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years of age or older Anterior circulation aneurysm Patients who have undergone surgical intervention Absence of rebleeding or new intracranial hemorrhage noted on post-intervention CT scan Consent for study participation Exclusion Criteria: Non-aneurysmal subarachnoid hemorrhage Multiple ruptured aneurysms Patients with congestive heart failure Severe aneurysmal subarachnoid hemorrhage (Hunt Hess Grade V) Active pathological bleeding Allergy to cilostazol Positive pregnancy test Coagulopathy not caused by anti-coagulant use History of hemorrhagic complications (gastrointestinal bleeding, etc) Uncontrolled or severe comorbidity that would qualify as an absolute contraindication for cilostazol Patients requiring anticoagulant/antiplatelet treatment following intervention (e.g. stent-assisted coiling or flow-diverting stent obliteration of aneurysm)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Implement standard treatment regimen of 60 mg nimodipine every 4 hours for 21 days and the standard aneurysmal subarachnoid treatment pathway. | Other: Placebo<br>* The standard treatment regimen of 60 mg nimodipine every 4 hours for 21 days and the standard aneurysmal subarachnoid treatment pathway<br>|
| Experimental: Experimental<br>Administer 100 mg cilostazol, twice daily for 14 days. In addition, implement the standard treatment regimen of 60 mg nimodipine every 4 hours for 21 days, and the standard aneurysmal subarachnoid treatment pathway. | Drug: Cilostazol 100 MG<br>* The addition of 100 mg cilostazol, twice daily for 14 days, to the standard treatment regimen of 60 mg nimodipine every 4 hours for 21 days and the standard aneurysmal subarachnoid treatment pathway<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Delayed Cerebral Infarction | Ischemic lesions demonstrated on follow-up CT or MRI will be interpreted as new cerebral infarctions | Baseline | 
| Delayed Cerebral Infarction | Ischemic lesions demonstrated on follow-up CT or MRI will be interpreted as new cerebral infarctions | 1 week (+/- 2 days) postoperatively | 
| Delayed Cerebral Infarction | Ischemic lesions demonstrated on follow-up CT or MRI will be interpreted as new cerebral infarctions | 1 month (+/- 7 days) postoperatively | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Symptomatic Cerebral Vasospasm | Development of a new focal or global neurological deficit or deterioration of at least 2 points on the Glasgow Coma Scale which was not explained by initial hemorrhage, re-bleeding, hydrocephalus, surgical complications, fever, infections, or electrolyte or metabolic disturbances; regardless of cerebral infarctions or angiographic vasospasm on imaging | At any point leading up to 14 days post-operation | 
| Radiographic Vasospasm | Arterial narrowing not attributable to atherosclerosis, catheter-induced vasospasm, or vessel hypoplasia | Between 7-10 days postoperatively | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Delayed cerebral ischemia, Cerebral vasospasm, Cilostazol