Evaluation of Intravenous Cardene(Nicardipine)and Labetalol Use in the Emergency Department (CLUE)

• ClinicalTrials.gov Identifier: NCT00765648
• Recruitment Status: Completed
• First Posted: October 3, 2008
• Results First Posted: December 11, 2014
• Last Update Posted: January 6, 2015
• Sponsor: The Cleveland Clinic
• Collaborator: EKR Therapeutics, Inc
• Information provided by (Responsible Party): The Cleveland Clinic

Tracking Information

• First Submitted Date: October 1, 2008
• First Posted Date: October 3, 2008
• Results First Submitted Date: July 18, 2011
• Results First Posted Date: December 11, 2014
• Last Update Posted Date: January 6, 2015
• Study Start Date: October 2008
• Actual Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 4, 2014)

Percentage of Subjects Achieving a Pre-defined Target Systolic Blood Pressure (BP) Within 30 Minutes. [ Time Frame: 30 minutes after initiation of therapy ]

Percentage of subjects achieving a pre-defined target systolic blood pressure (BP) range defined as a systolic blood pressure that is within +/- 20 mmHg of the target as established by the investigator.

• Original Primary Outcome Measures (submitted: October 2, 2008): Percentage of subjects achieving a pre-defined target systolic BP range defined as a systolic blood pressure that is within +/- 20 mmHg of the target as established by the investigator. [ Time Frame: 30 minutes after initiation of therapy ]

Current Secondary Outcome Measures (submitted: December 4, 2014)

• Average Number of Dose Titrations Within 30 Minutes [ Time Frame: 30 minutes ]
  Calculated as the mean (± standard deviation) number of titrations over 30 minutes for each treatment group
• Emergency Department(ED)Time to Disposition Decision [ Time Frame: 6 hours ]
  Median number of hours from hospital admission until Emergency Department(ED)disposition
• Treatment Failure [ Time Frame: 6 hours ]
  Treatment failure is defined as admission to the hospital or observation unit for BP management
• Subjects Requiring the Use of Intravenous Rescue Medications [ Time Frame: 6 hours ]
  The percent of subjects requiring the use of intravenous rescue medications
• Transition Time to Oral Medication [ Time Frame: 6 hours ]
  The median transition time (in hours) to oral medication

Original Secondary Outcome Measures (submitted: October 2, 2008)

• Variability in BP: Efficacy of BP control by comparing the AUC of BP-time curve between nicardipine and labetalol [ Time Frame: 6 hours ]
• Determine heart rate profile during treatment and during ED therapy [ Time Frame: 6 hours ]
• Number of dose titrations for Cardene I.V. versus labetalol within 30 minutes [ Time Frame: 6 hours ]
• ED time to disposition decision [ Time Frame: 6 hours ]
• Treatment failure as defined by admission to the hospital or observation unit for BP management [ Time Frame: 6 hours ]
• The percent of subjects requiring the use of IV rescue medications [ Time Frame: 6 hours ]
• Transition time to oral medication [ Time Frame: 6 hours ]
• Determine the pharmacoeconomic impact of the use of Cardene I.V. compared to labetalol [ Time Frame: 6 hours ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Evaluation of Intravenous Cardene(Nicardipine)and Labetalol Use in the Emergency Department
• Official Title: A Phase IV, Randomized Trial to Determine the Efficacy and Safety of Cardene Intravenous (I.V.) Versus Labetalol for Management of Hypertensive Emergencies in the Emergency Department Setting
• Brief Summary: The purpose of this study is to compare the safety and efficacy of Cardene I.V. to labetalol administered intravenously for the management of hypertension in the emergency department setting.

Detailed Description

More than 3 million patients yearly receive an intravenous antihypertensive agent in the US. Despite this large number of critically ill patients treated annually, little research exists in the area of acute severe hypertension, specifically hypertensive emergency, a serious condition that contributes to morbidity and mortality.

Two agents that are commonly used to treat acute hypertensive crisis include labetalol and nicardipine. Cardene may provide benefits in titration and has shown to have lower dosage adjustments compared to labetalol. Nicardipine has also shown a decreased need for additional antihypertensives when compared to labetalol in patients with stroke in a neurological ICU.

• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Hypertensive Urgency

Intervention

• Drug: nicardipine intravenous
  nicardipine intravenous 5 mg/hour titrated every 5 minutes by 2.5 mg/hour until target systolic blood pressure range (TSBPR) is reached or maximum dose of 15 mg/hour is achieved.Following achievement of target systolic blood pressure range the infusion rate should be decreased to 3 mg/hour
  Other Name: Nicardipine hydrochloride
• Drug: Labetalol
  Labetalol: bolus therapy to start at 20 mg intravenous injection over 2 minutes, may repeat 20mg, 40mg or 80mg injections every 10 minutes until target systolic blood pressure range(TSBPR)is reached or a maximum of 300 mg is injected.

Study Arms

• Active Comparator: 1
  nicardipine intravenous
  Intervention: Drug: nicardipine intravenous
• Active Comparator: 2
  Labetalol
  Intervention: Drug: Labetalol

Publications *

• Varon J, Soto-Ruiz KM, Baumann BM, Borczuk P, Cannon CM, Chandra A, Cline DM, Diercks DB, Hiestand B, Hsu A, Jois-Bilowich P, Kaminski B, Levy P, Nowak RM, Schrock JW, Peacock WF. The management of acute hypertension in patients with renal dysfunction: labetalol or nicardipine? Postgrad Med. 2014 Jul;126(4):124-30. doi: 10.3810/pgm.2014.07.2790.
• Cannon CM, Levy P, Baumann BM, Borczuk P, Chandra A, Cline DM, Diercks DB, Hiestand B, Hsu A, Jois P, Kaminski B, Nowak RM, Schrock JW, Varon J, Peacock WF. Intravenous nicardipine and labetalol use in hypertensive patients with signs or symptoms suggestive of end-organ damage in the emergency department: a subgroup analysis of the CLUE trial. BMJ Open. 2013 Mar 26;3(3):e002338. doi: 10.1136/bmjopen-2012-002338.
• Peacock WF, Varon J, Baumann BM, Borczuk P, Cannon CM, Chandra A, Cline DM, Diercks D, Hiestand B, Hsu A, Jois-Bilowich P, Kaminski B, Levy P, Nowak RM, Schrock JW. CLUE: a randomized comparative effectiveness trial of IV nicardipine versus labetalol use in the emergency department. Crit Care. 2011;15(3):R157. doi: 10.1186/cc10289. Epub 2011 Jun 27.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 2, 2008): 226
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: January 2010
• Actual Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• 18 years of age or older
• Systolic blood pressure ≥180 mm Hg on 2 consecutive readings(10 minutes apart)presenting in the emergency department (ED)

Exclusion Criteria:

• Use of any investigational drug within 1 month prior to emergency department (ED)
• Pregnant or breast-feeding females
• Contraindications or allergy to beta-blockers and calcium channel blockers (see FDA approved labeling for nicardipine intravenous and labetalol)
• Subjects with decompensated congestive heart failure (CHF) or with a known left ventricular ejection fraction (LVEF) <35%
• History of stroke within 30 days
• Known liver failure
• Suspected myocardial infarction
• Suspected aortic dissection
• Suspected cocaine overdose
• Concurrently receiving other intravenous (I.V.) hypertensive medications

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00765648
• Other Study ID Numbers: 2008-001
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: The Cleveland Clinic
• Original Responsible Party: W. Frank Peacock IV, MD, Vice Chair Research, Department of Emergency Medicine, Cleveland Clinic
• Current Study Sponsor: The Cleveland Clinic
• Original Study Sponsor: Same as current
• Collaborators: EKR Therapeutics, Inc

Investigators

• Principal Investigator: W. Frank Peacock, MD; The Cleveland Clinic
• Principal Investigator: Joseph Varon, MD; The University of Texas Health Science Center, Houston

• PRS Account: The Cleveland Clinic
• Verification Date: July 2011