Cerebral Vasospasm
Conditions
Keywords
Vasospasm, Subarachnoid hemorrhage, Aneurysmal subarachnoid hemorrhage, Nicardipine, Intrathecal, SAH, aSAH
Brief summary
The purpose of this study is to determine if intrathecal nicardipine is safe for the treatment of cerebral vasospasm.
Detailed description
Subarachnoid hemorrhage accounts for approximately 5% of all strokes and affects 30,000 Americans per year. Poor outcome from aneurysmal subarachnoid hemorrhage (SAH) occurs in 50 to 75% of patients, and this is attributed to secondary ischemia in approximately 30% of patients. This delayed cerebral ischemia has been attributed to the anatomic narrowing of arteries in the cerebral vasculature which occurs following SAH. Because of this relationship between cerebral vasospasm, cerebral ischemia, and poor outcome, there has been significant effort to establish treatments that decrease the incidence of vasospasm after SAH. Currently, medications and hemodynamic maneuvers are used as standard of care for the treatment of vasospasm and to improve outcome after SAH. The calcium channel blocker, nimodipine, is one of the few treatments for vasospasm that has been shown to be of proven benefit. Nicardipine is another calcium channel blocker that has been evaluated in several studies via an intravenous administration route. These studies did show significant improvements in symptomatic and angiographic vasospasm, although a benefit in outcome was not seen. However, the intravenous administration of nicardipine was associated with significant systemic side effects that may have affected outcome including hypotension, pulmonary edema, and azotemia. The administration of nicardipine via an intrathecal route avoids the systemic complications associated with intravenous dosing since the direct cerebrospinal fluid dosing is much lower. The result is that the systemic concentration will remain low avoiding systemic side effects, and central nervous system concentration will remain high. We propose that this difference may improve outcomes while minimizing complication related effects on patient outcomes.
Interventions
Nicardipine hydrochloride 4mg by intrathecal administration twice a day until post-hemorrhage day 10.
DRUGPreservative-free normal saline
Preservative-free normal saline 1.6 mL by intrathecal administration twice a day until post-hemorrhage day 10.
Sponsors
University of Florida
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female 18 years of age and older * Subarachnoid hemorrhage documented on head CT * Fisher Grade 3 or 4 * Hunt Hess Grade 1-5 * Cerebral aneurysm as definitive source of subarachnoid hemorrhage * Cerebral aneurysm must be treated via open or endovascular techniques * Presence of external ventricular drain * Written informed consent obtained from subject or subject's legally authorized representative
Exclusion criteria
* Absence or inability to have an external ventricular drain (coagulopathy) * Non-aneurysmal subarachnoid hemorrhage (perimesencephalic) * Untreated cerebral aneurysm * Inability to be randomized prior to post-hemorrhage day 4 * Elevated intra-cranial pressures that would preclude external ventricular drain clamping for 30-60 minutes * Inability to administer study medication (severe intra-ventricular hemorrhage, occluded external ventricular drain) * Inability to obtain angiography (coagulopathy, renal failure) * Pregnant * Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants With Bacterial Meningitis. | Day 1 of study drug until post-hemorrhage day 10. |
Secondary
| Measure | Time frame |
|---|---|
| Number of Participants With Cerebral Vasospasm. | Day 1 of study drug until post-hemorrhage day 10. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Nicardipine Hydrochloride Nicardipine hydrochloride 4mg by intrathecal administration twice a day until post-hemorrhage day 10.
Nicardipine hydrochloride: Nicardipine hydrochloride 4mg by intrathecal administration twice a day until post-hemorrhage day 10. | 1 |
| Preservative-free Normal Saline Preservative-free normal saline 1.6 mL by intrathecal administration twice a day until post-hemorrhage day 10.
Preservative-free normal saline: Preservative-free normal saline 1.6 mL by intrathecal administration twice a day until post-hemorrhage day 10. | 1 |
| Total | 2 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 0 |
| Overall Study | Physician Decision | 0 | 1 |
Baseline characteristics
| Characteristic | Nicardipine Hydrochloride | Preservative-free Normal Saline | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 1 Participants | 1 Participants |
| Region of Enrollment United States | 1 participants | 1 participants | 2 participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 1 | 1 / 1 |
| serious Total, serious adverse events | 1 / 1 | 0 / 1 |
Outcome results
Primary
Number of Participants With Bacterial Meningitis.
Time frame: Day 1 of study drug until post-hemorrhage day 10.
Population: Number of participants were not sufficient to perform data analysis.
Secondary
Number of Participants With Cerebral Vasospasm.
Time frame: Day 1 of study drug until post-hemorrhage day 10.
Population: Number of participants were not sufficient to perform data analysis.