Safety Study of Nicardipine to Treat Cerebral Vasospasm

Cerebral Vasospasm Clinical Trial

Official title:

Intraventricular Nicardipine for the Treatment of Cerebral Vasospasm: Prospective Pilot Study

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01810302
• Other study ID #: 034-2013
• Status: Terminated
• Phase: Phase 2
• First received: March 11, 2013
• Last updated: August 18, 2014
• Start date: August 2013
• Est. completion date: January 2014

Study information

• Verified date: August 2014
• Source: University of Florida
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine if intrathecal nicardipine is safe for the treatment of cerebral vasospasm.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 2
• Est. completion date: January 2014
• Est. primary completion date: January 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cerebral Vasospasm
• Vasospasm, Intracranial

Intervention

Drug:
• Nicardipine hydrochloride
Nicardipine hydrochloride 4mg 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.

Locations

Country	Name	City	State
United States	University of Florida	Gainesville	Florida

Sponsors (1)

Lead Sponsor	Collaborator
University of Florida

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Bacterial Meningitis.		Day 1 of study drug until post-hemorrhage day 10.	Yes
Secondary	Number of Participants With Cerebral Vasospasm.		Day 1 of study drug until post-hemorrhage day 10.	No