A Pilot Study to Evaluate Efficacy and Safety of Clevidipine in Neurosurgical Patients

• Sponsor: NYU Langone Health (Other)
• Overall Status: Completed
• CT.gov ID: NCT00952081
• Collaborator: The Medicines Company (Industry)
• Enrollment: 22
• Location: 1
• Arm: 1
• Duration (Months): 7.1
• Patients Per Site Per Month: 3.1

Study Details

Study Description

Brief Summary

This protocol describes a study to gain experience in the use of Clevidipine for perioperative blood pressure control in patients undergoing craniotomy for brain tumor or epilepsy focus resection. The purpose of this study is to establish the efficacy of Clevidipine for intraoperative blood pressure control in patients undergoing intracranial procedures, and gather information on the dosage and adverse effects of Clevidipine in neurosurgical patients. This initial pilot experience serves to familiarize the investigators with the use of this drug prior to initiating a planned randomized trial versus institutional standard-of-care therapy. The investigators will obtain greater familiarity with the dosing of clevidipine in this patient population and collect information on the incidence of adverse effects.

Condition or Disease	Intervention/Treatment	Phase
Hypertension; Brain Tumor; Epilepsy	Drug: Clevidipine	Phase 4

Detailed Description

Clevidipine, a recently introduced, short-acting, vascular-selective calcium antagonist, could be a potentially useful adjuvant for neurosurgical cases. It decreases arterial blood pressure by reducing systemic vascular resistance with no effect on venous capacitance vessels (7). Clevidipine was successfully used for the treatment of hypertension in cardiac surgical patients (8). However, there is no information available on its efficacy and safety in patients undergoing intracranial surgery.

The perioperative course of patients undergoing intracranial surgery is frequently complicated by acute hypertensive episodes. Acute hypertension in neurosurgical patients is associated with intracranial bleeds and prolonged hospital stay (1). Even with current neuroanesthesia management, hemodynamic stability may be challenging, especially in hypertensive patients. An anesthetic technique that improves perioperative hemodynamics without increasing the incidence of undesirable events (such as increased intracranial pressure, prolonged recovery, etc.) is desirable.

A number of antihypertensive agents are available to treat perioperative hypertension. Labetalol is commonly used to treat hypertensive episodes in patients undergoing craniotomy, but may not be desirable in certain patient populations because of its low potency, a slow onset of peak effect (2), and unpredictability in dose requirements (3). Esmolol is only mildly effective in treating postoperative hypertension. Perioperative use is further complicated by bradycardia and conduction delay. Nicardipine is more effective than esmolol in controlling postoperative hypertension (4). However, it causes a dose-dependent cerebral vasodilation, inhibition of autoregulation, as well as a high incidence of hypotension (as compared to labetalol) (5). Hydralazine may increase intracranial pressure by as much as 100% and is rarely used as the sole agent in treating hypertension in neurosurgical patients (6).

Study Design

• Study Type: Interventional
• Actual Enrollment: 22 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Pilot Study to Evaluate Efficacy and Safety of Clevidipine in Neurosurgical Patients
• Study Start Date: Jul 1, 2009
• Actual Primary Completion Date: Dec 1, 2009
• Actual Study Completion Date: Feb 1, 2010

Arms and Interventions

Arm

Intervention/Treatment

Experimental: clevidipine,brain tumor,hypertension 21 or older, Clevidipine in brain tumor resection, epilepsy focus resection during acute hypertension under general anesthesia

Drug: Clevidipine; Clevidipine (0.5 mg/ml in 20 % lipid solution) will be administered via peripheral vein using syringe pump; drug infusion will be initiated at 5 mg/hr (10ml/h) and titrated to effect up to a maximum rate of 32 mg/hr when SBP exceeds 130 mm Hg. The anesthesiologist will be allowed to administer the alternative antihypertensive treatment (e.g. labetalol, hydralazine) after achieving a maximum clevidipine infusion rate.; Other Names: Cleviprex Clevidipine butyrate

Outcome Measures

Primary Outcome Measures

1. The Primary Endpoint of This Trial is the Proportion of Patients Who Did Not Require Rescue Antihypertensive Medication to Maintain SBP Below 130 mmHg (i.e. Clevidipine is a Sole Antihypertensive Agent Used for Blood Pressure Control) [intraoperatively and 90 min after surgery]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Age 21 or older

• Able to give consent

• No significant laboratory abnormalities

• Undergoing elective surgery for tumor resection or epilepsy focus resection

Exclusion Criteria:

• Patients with acute cardiac ischemia, renal or liver dysfunction, unstable hemodynamic, advanced heart block, or pregnancy defective lipid metabolism such as pathologic hyperlipemia, lipoid nephrosis, or acute pancreatitis if it is accompanied by hyperlipidemia; and in patients with severe aortic stenosis will be excluded.

• Known or suspected allergy to study drug or study drug components,patients with allergies to soybeans, soy products, eggs, or egg products; Participation in other clinical research studies involving the evaluation of other investigational drugs or devices within 30 days of enrollment in this study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	NYU Langone Medical Center, Department of Anesthesiology	New York	New York	United States	10016

Sponsors and Collaborators

• NYU Langone Health
• The Medicines Company

Investigators

• Principal Investigator: Alex Bekker, MD, PhD, NYU School of Medicine

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• pubmed abstract

Publications

None provided.

• Responsible Party: NYU Langone Health
• ClinicalTrials.gov Identifier: NCT00952081
• Other Study ID Numbers: 08-745
• First Posted: Aug 4, 2009
• Last Update Posted: Feb 9, 2015
• Last Verified: Jan 1, 2015

• Keywords provided by NYU Langone Health: Hypertension; Neurosurgery; bloodpressure control; brain tumor resection; epilepsy focus resection
• Additional relevant MeSH terms: Brain Neoplasms; Epilepsy; Hypertension; Clevidipine

Study Results

Participant Flow

Recruitment Details	Patients scheduled for intracranial surgery were prospectively enrolled after giving consent. Clevidipine (0.5 mg/mL in 20% lipid solution, which was to be initiated at 10 mg/h and titrated to effect) was administered as the primary antihypertensive agent for perioperative hypertension, with target BPs of less than 130mm Hg.

Arm/Group Title	Clevidipine,Brain Tumor,Hypertension
Arm/Group Description	Clevidipine(0.5 mg/mL in 20% lipid solution), initiated at 10 mg/h and titrated to effect, was administered as the primary antihypertensive agent for perioperative hypertension, with target BPs of less than 130mm Hg.
Period Title: Overall Study
STARTED	22
COMPLETED	22
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Clevidipine,Brain Tumor,Hypertension
Arm/Group Description	21 or older, Clevidipine in brain tumor resection, epilepsy focus resection during acute hypertension under general anesthesia
Overall Participants	22
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	21 95.5%
>=65 years	1 4.5%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54 (14.25)
Sex: Female, Male (Count of Participants)
Female	12 54.5%
Male	10 45.5%
Region of Enrollment (participants) [Number]
United States	22 100%

Outcome Measures

1. Primary Outcome

Title	The Primary Endpoint of This Trial is the Proportion of Patients Who Did Not Require Rescue Antihypertensive Medication to Maintain SBP Below 130 mmHg (i.e. Clevidipine is a Sole Antihypertensive Agent Used for Blood Pressure Control)
Time Frame	intraoperatively and 90 min after surgery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Clevidipine,Brain Tumor,Hypertension
Arm/Group Description	21 or older, Clevidipine in brain tumor resection, epilepsy focus resection during acute hypertension under general anesthesia
Measure Participants	22
Number [participants]	21 95.5%

Adverse Events

Adverse Event Reporting Description	Only Adverse Events attributed to study drug (clevidipine) were reported.
Arm/Group Title	Clevidipine,Brain Tumor,Hypertension
Arm/Group Description	21 or older, Clevidipine in brain tumor resection, epilepsy focus resection during acute hypertension under general anesthesia
All Cause Mortality
	Clevidipine,Brain Tumor,Hypertension
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Clevidipine,Brain Tumor,Hypertension
	Affected / at Risk (%)	# Events
Total	0/22 (0%)
Other (Not Including Serious) Adverse Events
	Clevidipine,Brain Tumor,Hypertension
	Affected / at Risk (%)	# Events
Total	0/22 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.