Safety Study of Nicardipine to Treat Cerebral Vasospasm

• ClinicalTrials.gov Identifier: NCT01810302
• Recruitment Status: Terminated
• First Posted: March 13, 2013
• Results First Posted: August 29, 2014
• Last Update Posted: August 29, 2014
• Sponsor: University of Florida
• Information provided by (Responsible Party): University of Florida

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Cerebral Vasospasm	Drug: Nicardipine hydrochloride; Drug: Preservative-free normal saline	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 2 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Intraventricular Nicardipine for the Treatment of Cerebral Vasospasm: Prospective Pilot Study
• Study Start Date: August 2013
• Actual Primary Completion Date: January 2014
• Actual Study Completion Date: January 2014

Arms and Interventions

Arm	Intervention/treatment
Experimental: Nicardipine hydrochloride; Nicardipine hydrochloride 4mg by intrathecal administration twice a day until post-hemorrhage day 10.	Drug: Nicardipine hydrochloride; Nicardipine hydrochloride 4mg by intrathecal administration twice a day until post-hemorrhage day 10.; Other Names: Nicardipine; Cardene
Placebo Comparator: Preservative-free normal saline; Preservative-free normal saline 1.6 mL by intrathecal administration twice a day until post-hemorrhage day 10.	Drug: Preservative-free normal saline; Preservative-free normal saline 1.6 mL by intrathecal administration twice a day until post-hemorrhage day 10.; Other Names: Normal saline; Placebo; NS

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Bacterial Meningitis. [ Time Frame: Day 1 of study drug until post-hemorrhage day 10. ]

Secondary Outcome Measures :

1. Number of Participants With Cerebral Vasospasm. [ Time Frame: Day 1 of study drug until post-hemorrhage day 10. ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Florida

University of Florida

Gainesville, Florida, United States, 32610

Sponsors and Collaborators

University of Florida

Investigators

• Principal Investigator: Spiros L. Blackburn, MD; University of Florida

More Information

• Responsible Party: University of Florida
• ClinicalTrials.gov Identifier: NCT01810302
• Other Study ID Numbers: 034-2013
• First Posted: March 13, 2013
• Results First Posted: August 29, 2014
• Last Update Posted: August 29, 2014
• Last Verified: August 2014

Keywords provided by University of Florida:

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

Additional relevant MeSH terms:

Vasospasm, Intracranial; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Nicardipine; Antihypertensive Agents; Calcium Channel Blockers; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Calcium-Regulating Hormones and Agents; Physiological Effects of Drugs; Vasodilator Agents