Safety Study of Nicardipine to Treat Cerebral Vasospasm

NCT ID: NCT01810302

Last Updated: 2014-08-29

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 2 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-08-31
• Study Completion Date: 2014-01-31

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.

Conditions

Cerebral Vasospasm

Keywords

Vasospasm; Subarachnoid hemorrhage; Aneurysmal subarachnoid hemorrhage; Nicardipine; Intrathecal; SAH; aSAH

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Nicardipine hydrochloride

Nicardipine hydrochloride 4mg by intrathecal administration twice a day until post-hemorrhage day 10.

Group Type: EXPERIMENTAL

Nicardipine hydrochloride

Intervention Type: DRUG

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.

Group Type: PLACEBO_COMPARATOR

Preservative-free normal saline

Intervention Type: DRUG

Preservative-free normal saline 1.6 mL by intrathecal administration twice a day until post-hemorrhage day 10.

Interventions

Nicardipine hydrochloride

Nicardipine hydrochloride 4mg by intrathecal administration twice a day until post-hemorrhage day 10.

Intervention Type: DRUG

Preservative-free normal saline

Preservative-free normal saline 1.6 mL by intrathecal administration twice a day until post-hemorrhage day 10.

Intervention Type: DRUG

Other Intervention Names

Nicardipine; Cardene; Normal saline; Placebo; NS

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Florida

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Spiros L. Blackburn, MD

Role: PRINCIPAL_INVESTIGATOR

University of Florida

Locations

University of Florida

Gainesville, Florida, United States

Countries

United States

Other Identifiers

034-2013

Identifier Type: -

Identifier Source: org_study_id