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Clevidipine in the Treatment of Patients With Acute Hypertension and Intracerebral Hemorrhage (ACCELERATE)
This study is currently recruiting participants.
Verified by The Medicines Company, January 2009
Sponsored by: The Medicines Company
Information provided by: The Medicines Company
ClinicalTrials.gov Identifier: NCT00666328
  Purpose

The purpose of this study is to determine the efficacy and safety of clevidipine for treating acute hypertension (high blood pressure, defined as systolic blood pressure >160 mmHg) in patients with intracerebral hemorrhage (i.e., bleeding in the brain; stroke).


Condition Intervention Phase
Hypertension
Hemorrhage
Drug: Clevidipine butyrate injectable emulsion
Phase III

MedlinePlus related topics: High Blood Pressure
Drug Information available for: Calcium gluconate Clevidipine Lipids
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Official Title: The Evaluation of Patients With Acute Hypertension and Intracerebral Hemorrhage With Intravenous Clevidipine Treatment

Further study details as provided by The Medicines Company:

Primary Outcome Measures:
  • The median time to achieve the target BP (systolic blood pressure ≤160 mmHg to ≥140 mmHg) within 30 minutes of the initiation of clevidipine infusion. [ Time Frame: Within 30 minutes of the initiation of study drug infusion ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The percentage of patients who reach a systolic blood pressure of ≤160 mmHg within 30 minutes of the initiation of clevidipine infusion [ Time Frame: Within 30 minutes of the initiation of study drug infusion ] [ Designated as safety issue: No ]
  • Percent change from baseline in systolic blood pressure during the initial 30 minutes of clevidipine infusion [ Time Frame: During the initial 30 minutes of study drug infusion ] [ Designated as safety issue: No ]
  • Magnitude, frequency and duration of systolic blood pressure excursions (calculated as area under the curve) outside the target range normalized per hour for the duration of the clevidipine monotherapy infusion [ Time Frame: Duration of the study drug infusion (up to 96 hours) ] [ Designated as safety issue: No ]
  • Percent time blood pressures were maintained within the target range (systolic blood pressure ≤160 mmHg to ≥140 mmHg) over each 24 hours during monotherapy infusion of clevidipine [ Time Frame: Every 24 hours (for up to 96 hours) ] [ Designated as safety issue: No ]
  • Mean and median dose of clevidipine during the treatment period [ Time Frame: Up to 96 hours ] [ Designated as safety issue: No ]
  • Proportion of patients requiring the addition of an alternative antihypertensive agent(s) with or without clevidipine [ Time Frame: Up to 96 hours ] [ Designated as safety issue: No ]
  • Percent change in heart rate during the initial 30 minutes of clevidipine infusion [ Time Frame: During initial 30 minutes of study drug infusion ] [ Designated as safety issue: Yes ]
  • The percentage of patients whose systolic blood pressure is less than <90 mmHg within 30 minutes of the initiation of clevidipine infusion [ Time Frame: Within 30 minutes of the initiation of study drug infusion ] [ Designated as safety issue: Yes ]
  • Safety of a prolonged infusion of clevidipine (up to 96 hours) [ Time Frame: Up to 7 days following termination of study drug infusion ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 60
Study Start Date: April 2008
Estimated Study Completion Date: August 2009
Estimated Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1: Experimental Drug: Clevidipine butyrate injectable emulsion

Clevidipine butyrate injectable emulsion (0.5 mg/mL in 20% lipid emulsion; 100 mL bottles) will be administered intravenously to all patients via a single dedicated line.

Clevidipine will be infused at an initial rate of 2.0 mg/h for the first 1.5 minutes. Thereafter, titration to higher infusion rates can be attempted as needed to obtain the target systolic blood pressure (SBP) range (SBP ≤160 mmHg to ≥140 mmHg). Titration to effect is to proceed by doubling the dose every 1.5 minutes, up to a maximum of 32.0 mg/h, until the desired effect (SBP within the target range) is attained.

Clevidipine infusion may continue for up to a maximum of 96 hours. Patients will be followed for 7 days following termination of the clevidipine infusion.


Detailed Description:

This is a multicenter, single-arm, non-blinded dose titration efficacy and safety trial evaluating the ability of clevidipine, a vascular-selective L-type calcium channel antagonist, to rapidly control acute hypertension in patients with intracerebral hemorrhage. Informed consent will be obtained from patients meeting the inclusion criteria before the initiation of any study-specific procedures. At screening a clinical and neurological examination will be carried out. For the purposes of this study, acute hypertension will be defined as SBP >160 mmHg immediately prior to initiation of study drug. Patients with and an intracerebral hemorrhage (ICH) volume ≤60 cc as well those with an ICH volume >60 cc will be enrolled. Infusion of study drug will be initiated within 6 hours of ICH symptom onset. All eligible patients will be enrolled to receive clevidipine in an open label manner. Clevidipine will be infused at an initial rate of 2.0 mg/h for the first 1.5 minutes. Thereafter, titration to higher infusion rates can be attempted as needed to obtain the target SBP range (SBP ≤160 mmHg to ≥140 mmHg). Titration to effect is to proceed by doubling the dose every 1.5 minutes, up to a maximum of 32.0 mg/h, until the desired effect (SBP within the target range) is attained. Clevidipine infusion may continue for up to a maximum of 96 hours. Twenty-four hour follow-up CT scan results will be recorded, including measurement of intracerebral and intraventricular hematoma volumes and measurement of perihematoma edema volume. Assessment of safety will be performed throughout the treatment period and until 6 hours after termination of study drug. Patients will be followed for 7 days following termination of the clevidipine infusion.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • CT evidence of intracerebral hemorrhage (diagnosis within 6 hours of symptom onset)
  • Age 18 years or older
  • Baseline systolic blood pressure (immediately prior to initiation of clevidipine) >160 mmHg measured using an arterial line
  • Requires antihypertensive therapy to achieve systolic blood pressure ≤160 mmHg
  • Written informed consent

Exclusion Criteria:

  • Decision for early surgical evacuation (e.g., large cerebellar or lobar hemorrhage)
  • Receipt of an oral antihypertensive within 2 hours prior to initiation of clevidipine
  • Treatment with a continuous infusion of an IV antihypertension agent prior to initiation of clevidipine. Bolus treatment with labetalol or hydralazine is permitted
  • Intracerebral hematoma considered to be related to trauma by the neurologist or neurosurgeon
  • Aneurysmal sub-arachnoid hemorrhage
  • Glasgow coma score of <5 and fixed dilated pupils
  • Expectation that the patient will not tolerate or require intravenous antihypertensive therapy for a minimum of 30 minutes
  • Coagulopathy (international normalization ratio >1.3 at screening)
  • Known or suspected aortic dissection
  • Acute myocardial infarction on presentation
  • Positive pregnancy test or known pregnancy
  • Intolerance or allergy to calcium channel blockers
  • Allergy to soybean oil or egg lecithin
  • Known liver failure, cirrhosis or pancreatitis
  • Prior directives against advanced life support
  • Participation in other clinical research studies involving the evaluation of other investigational drugs or devices within 30 days of enrollment
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00666328

Contacts
Contact: Linda Rootkin 973-647-6093 Linda.Rootkin@themedco.com
Contact: Leisa Waynick 973-647-6082 Leisa.Waynick@themedco.com

Locations
United States, District of Columbia
Washington Hospital Center Recruiting
Washington, District of Columbia, United States, 20010-2975
Contact: Daniel L Herr, MS, MD, FCCM     202-877-7259     daniel.l.herr@Medstar.net    
Contact: Nazli Bolouri, MD     (202) 877-2058     Nazli.Bolouri@MedStar.net    
Principal Investigator: Daniel L Herr, MS MD FCCM            
United States, Hawaii
The Queens Medical Center Recruiting
Honolulu, Hawaii, United States, 96813
Contact: Cherylee Chang, MD     808-537-7152     cchang@queens.org    
Contact: Tracy Stern, RN, CCRC     808-537-7175     tstern@queens.org    
Principal Investigator: Cherlylee Chang, MD            
United States, Maryland
The John Hopkins Hospital Recruiting
Baltimore, Maryland, United States, 21287
Contact: Romergryko Geocadin, MD     410-955-7481     rgeocadi@jhmi.edu    
Contact: Shannon N LeDroux, B.Sc.     (410) 502-0505     sledrou1@jhmi.edu    
Principal Investigator: Romergryko Geocadin, MD            
United States, New York
Columbia University Medical Center Recruiting
New York, New York, United States, 10032
Contact: Kiwon Lee, MD     212-305-7236     kl2356@columbia.edu    
Contact: Noeleen Ostapkovich, MS     212-305-4234     NOstapkovich@neuro.columbia.edu    
Principal Investigator: Kiwon Lee, MD            
United States, North Carolina
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27710
Contact: Carmelo Graffagnino, MD     919-684-5650     graff002@mc.duke.edu    
Contact: Joanna Stoner, BSN     919-668-5275     stone034@mc.duke.edu    
Principal Investigator: Carmelo Graffagnino, MD            
Guilford Neurologic - Moses H Cone Health System Recruiting
Greensboro, North Carolina, United States, 27405
Contact: James Love, MD     336-273-2511        
Contact: Patricia Henderson     336-273-2511     PHenderson@guilfordneurologic.com    
Principal Investigator: James Love, MD            
United States, Ohio
Cleveland Clinic Hospitals Recruiting
Cleveland, Ohio, United States, 44195
Contact: Gwendolyn Lynch, MD     216-312-4659     lynchg@ccf.org    
Contact: Rebecca Forkapa, RN     800-223-2273 ext 54488     forkapr@ccf.org    
Principal Investigator: Gwendolyn Lynch, MD            
The Ohio State University Recruiting
Columbus, Ohio, United States, 43210
Contact: Sergio D Bergese, MD     614-293-9027     bergese.1@osumc.edu    
Contact: Erika Puente, MD     614-366-8399     erika.puente@osumc.edu    
Principal Investigator: Sergio D Bergese, MD            
United States, Texas
The University Health Science Center at S.A. Recruiting
San Antonio, Texas, United States, 78229-3900
Contact: Anne D Leonard, BSN MPH     210-567-5625     LEONARDA@uthscsa.edu    
Contact: Augusto Parra, MD, MPH     210-567-5581     ParraA3@uthscsa.edu    
Principal Investigator: Augusto Parra, MD, MPH            
University of Texas Health Science Center at Houston Not yet recruiting
Houston, Texas, United States, 77030
Contact: David J Robinson, MD MS FACEP     713-500-7875     david.j.robinson@uth.tmc.edu    
Contact: Many Robers, DrPH, MPH     713-500-7661     mandy.j.robers@uth.tmc.edu    
Principal Investigator: David J Robinson, MD MS FACEP            
United States, Utah
Intermountain Medical Center Recruiting
Murray, Utah, United States, 84157
Contact: Ben Briggs     801-507-4753     ben.briggs@imail.org    
Contact: Angela Schwab, MS CGS     801-507-4753     angela.schwabb@imail.org    
Principal Investigator: John Zurasky, MD            
Germany
Universitatsklinikum Erlangen Recruiting
Erlangen, Germany, D91054
Contact: Stefan Schwab, MD     49-9131-85-36597     stefan.schwab@uk-erlangen.de    
Contact: Andrea-Maria Schickert-Schleicher, RN     49-9131-85-34673     andrea.schickert-schleicher@uk-erlangen.de    
Principal Investigator: Stefan Schwab, MD            
Ruprech-Karls University Not yet recruiting
Heidelberg, Germany, D69120
Contact: Thorsten Steiner, MD     06221-56-37531     thorsten_steiner@med.uni-heidelberg.de    
Contact: Pia Petra Schnitzer     06221-56-5496     pia.schnitzer@med.uni-heidelberg.de    
Principal Investigator: Thorsten Steiner, MD            
Germany, LEIPZIG
Universitätsklinikum Leipzig Recruiting
Liebigstraße 22a, LEIPZIG, Germany, D-04103
Contact: Daniela Urban     49-341-97-24206     daniela.urban@medizin.uni-leipzig.de    
Contact: Ines Gerhardt     49-341-97-24206     ines.gerhardt@medizin.uni-leipzig.de    
Principal Investigator: Dietmar Schneider, Prof Dr med habil            
Sponsors and Collaborators
The Medicines Company
Investigators
Principal Investigator: Carmelo Graffagnino, MD Duke University
  More Information

Responsible Party: The Medicines Company ( Linda Rootkin, Project Leader )
Study ID Numbers: TMC-CLV-07-02
Study First Received: April 22, 2008
Last Updated: January 5, 2009
ClinicalTrials.gov Identifier: NCT00666328  
Health Authority: United States: Food and Drug Administration;   United States: Institutional Review Board;   Germany: Federal Institute for Drugs and Medical Devices;   Germany: Ethics Commission

Keywords provided by The Medicines Company:
Hypertension
Hemorrhage
Antihypertensive Agent
Calcium Channel Blocker

Study placed in the following topic categories:
Calcium, Dietary
Cerebral Hemorrhage
Vascular Diseases
Central Nervous System Diseases
Intracranial Hemorrhages
Brain Diseases
Hemorrhage
Cerebrovascular Disorders
Hypertension

Additional relevant MeSH terms:
Pathologic Processes
Nervous System Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on January 16, 2009