Aneurysmal Subarachnoid Hemorrhage, Vasospasm
Conditions
Keywords
Aneurysmal Subarachnoid Hemorrhage, Vasospasm, Delayed cerebral ischemia, Nicardipine, Intrathecal injection
Brief summary
To investigate whether patients with cerebral vasospasm associated with aneurysmal subarachnoid hemorrhage have a better prognosis with intrathecal nicardipine injection via extraventricular drainage or lumbar drainage.
Detailed description
Objective: To investigate whether patients with cerebral vasospasm associated with aneurysmal subarachnoid hemorrhage have a better prognosis with intrathecal nicardipine injection via extraventricular drainage or lumbar drainage. Design: This study is a multi-center, prospective, double-blinded, randomized controlled trial. Interventions: First, 6 ml of cerebrospinal fluid is withdrawn from the EVD or LD catheter, and then 4 ml of nicardipine hydrochloride is injected into the EVD or LD drain tube, followed by 2 ml of 0.9 % sodium chloride solution (NaCl), and then the EVD or LD tube was clamped for 2 hours after the injection was completed, then kept open as clinically necessary until the next dose (twice a day).
Interventions
DRUGIntrathecal Nicardipine
First, 6 ml of cerebrospinal fluid is withdrawn from the EVD or LD catheter, and then 4 ml (4mg) of nicardipine is injected into the EVD or LD drain tube, followed by 2 ml normal saline solution, and then the EVD or LD tube is clamped for 2 hours, and then kept open as clinically necessary until the next dose (q12h) of medication.
OTHERNo intervention
A simulated intrathecal administration operation is performed by a dedicated physician who is unblinded to the group assignment, the EVD or LD tube is not opened, and no drug is given. The simulated administration process needs to be out of the patient's view (if awake patient) and out of the presence of study team personnel.
Sponsors
The Affiliated Hospital Of Guizhou Medical University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
The assigned intervention will be performed only by a separate unblinded dedicated physician who signs the confidential agreement. The attending/investigating physician and patient are blinded to the intervention assignment.
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Age 18-80. 2. Spontaneous SAH confirmed by head CT. 3. Saccular brain aneurysm is identified and treated, either surgically or endovascularly. 4. SAH Fisher grade \>1 or modified Fisher grade \>0. 5. EVD placed for acute hydrocephalus, or LD placed for draining bloody CSF as deemed necessary by the treating physician. 6. Any clinical scenario leading to the diagnosis of possible vasospasm, which includes: 1. Mean flow velocity of MCA \>120, or Lindegaard Ratio ( LR ) \> 3. 2. Any intracranial artery including MCA, ACA, PCA, and BA, TCD showed an upward trend of mean flow velocity for 2 consecutive days (\>25cm/s/day). 3. Clinical deterioration including mental status change (GCS score decrease \> 2) and focal neurological deficit unable to be attributed to other known neurological reasons. 4. Evidence of vasospasm on CTA or DSA, or ischemic change by CTP, MRI. 7. Within 14 days of onset of SAH. 8. Informed consent obtained from the patient or family member.
Exclusion criteria
1. Hunt-Hess Grade 5 or WFNS Grade 5 (no clinical improvement after EVD placement for acute hydrocephalus). 2. Bacterial or distal aneurysms without subarachnoid hemorrhage in the basal cisterns. 3. The treating physician determines that the culprit aneurysm has not been fully repaired, with a very high likelihood of rebleeding in the near term. 4. History of head trauma within the past 3 months. 5. Any recent brain disease within 3 months, such as tumors, stroke, epilepsy, vasculitis, arteriovenous malformation, hydrocephalus, etc. 6. History of psychiatric disorders or seizures within 3 months. 7. Severe concurrent medical conditions. 8. Pregnant women or those of childbearing potential with a positive urine or serum β-human chorionic gonadotropin (HCG) test. 9. Lactating women. 10. Life expectancy of less than 1 year prior to aSAH onset. 11. Pre-morbid mRS score \>1. 12. Participation in another randomized clinical trial that may confound the evaluation of this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dichotomized Modified Rankin Scale (mRS) 0-2 vs 3-6 | Day 90±30, Day 365±60. | The percentage of patients with mRS 0-2 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of CSF infection | Day 30±7 | Diagnosed with fever, positive CSF test including culture. |
| Rate of any type of new intracranial hemorrhage. | Day 90±30, Day 365±60. | The incidence of CSF shunt surgery |
| Dichotomized Modified Rankin Scale (mRS) 0-3 vs 4-6 | Day 90±30, Day 365±60. | The percentage of patients with mRS 0-3 |
| Mini-Mental State Examination (MMSE) score | Day 90±30, Day 365±60. | Minimum score 0 and maximum score 30 with higher score being better outcome |
| Change of National Institutes of Health Stroke Scale (NIHSS) score | At discharge | NIHSS Scores range from 0 - 42 with higher score being worse outcome |
| Cerebrospinal fluid shunt surgery rate | Day 90±30, Day 365±60. | The incidence of CSF shunt surgery |
| Overall mortality rate | Day 90±30, Day 365±60. | All etiology of mortality |
| Extended Glasgow Outcome Score (GOS-E). | Day 90±30, Day 365±60. | Minimum score 1 and maximum score 8 with higher number being better outcome |
| Modified Rankin Scale ordinal shift with mRS 5 and 6 combined | Day 90±30, Day 365±60. | Shift analysis looks at transitions across different levels of mRS score, shifting from higher score to lower score means favorable outcome |
| Adverse Event | Baseline, Day 2-21, Day 90±30, Day 365±60. | From enrollment to the end of the study, any event meeting the definition of adverse event (AE) was defined as an adverse event, and each occurrence was recorded in a separate adverse event table. |
| Serious Adverse Event | Baseline, Day 2-21, Day 90±30, Day 365±60. | During the period from enrollment to the end of the study, any event meeting the definition of serious adverse event (SAE) was defined as serious adverse event, and each occurrence was recorded by a separate adverse event table. |
Countries
China
Contacts
Primary ContactGuangtang Chen, MD
Outcome results
None listed