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

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Hypertensive Urgency
• Interventions: Drug: nicardipine intravenous; Drug: Labetalol
• Enrollment: 226

Participant Flow

Recruitment Details	Eligible patients had 2 systolic blood pressures(BP) measures > 180 mmHg at least 10 minutes apart, and no contraindications.Emergency room setting.
Pre-assignment Details

Arm/Group Title	Nicardipine Dosing Was 5 mg/Hour	Bolus Labetalol Began at 20 mg Over 2 Minutes
Arm/Group Description	nicardipine intravenous	Labetalol
Period Title: Overall Study
Started	110	116
Completed	109	114
Not Completed	1	2

Baseline Characteristics

Arm/Group Title		Nicardipine Dosing Was 5 mg/Hour	Bolus Labetalol Began at 20 mg Over 2 Minutes	Total
Arm/Group Description		nicardipine intravenous	Labetalol	Total of all reporting groups
Overall Number of Baseline Participants		110	116	226
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	110 participants	116 participants	226 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	81 73.6%	98 84.5%	179 79.2%
	>=65 years	29 26.4%	18 15.5%	47 20.8%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	110 participants	116 participants	226 participants
	Female	60 54.5%	59 50.9%	119 52.7%
	Male	50 45.5%	57 49.1%	107 47.3%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	110 participants	116 participants	226 participants
		110	116	226

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Intent to treat cohort.

Arm/Group Title	Nicardipine	Labetalol
Arm/Group Description:	Nicardipine was administered at 5mg/hour and increased every 5 minutes by 2.5 mg/hour until the target systolic blood pressure (SBP) range is reached or maximum of 15mg/hour is achieved.	Labetalol is given intravenous bolus starting with 20mg over 2 minutes, which is repeated at 20, 40, or 80mg injections every 10 minutes until the target systolic blood pressure (SBP) range is reached or a maximum of 300mg is administered.
Overall Number of Participants Analyzed	109	114
Measure Type: Number; Unit of Measure: percentage of participants
	91.7	82.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nicardipine, Labetalol
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.04
	Comments	[Not Specified]
	Method	Chi-squared
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-9.3
	Confidence Interval	(2-Sided) 95%; -18.0 to -0.6
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Average Number of Dose Titrations Within 30 Minutes
Description	Calculated as the mean (± standard deviation) number of titrations over 30 minutes for each treatment group
Time Frame	30 minutes

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nicardipine	Labetalol
Arm/Group Description:	Nicardipine was administered at 5mg/hour and increased every 5 minutes by 2.5 mg/hour until the target systolic blood pressure (SBP) range is reached or maximum of 15mg/hour is achieved.	Labetalol is given intravenous bolus starting with 20mg over 2 minutes, which is repeated at 20, 40, or 80mg injections every 10 minutes until the target systolic blood pressure (SBP) range is reached or a maximum of 300mg is administered.
Overall Number of Participants Analyzed	109	114
Mean (Standard Deviation); Unit of Measure: number of titrations
	2.2 (1)	1.3 (0.97)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nicardipine, Labetalol
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	t-test, 2 sided
	Comments	[Not Specified]

3. Secondary Outcome

Title	Emergency Department(ED)Time to Disposition Decision
Description	Median number of hours from hospital admission until Emergency Department(ED)disposition
Time Frame	6 hours

Outcome Measure Data

Analysis Population Description

these are the correct participant numbers for this secondary analysis

Arm/Group Title	Nicardipine	Labetalol
Arm/Group Description:	Nicardipine was administered at 5mg/hour and increased every 5 minutes by 2.5 mg/hour until the target systolic blood pressure (SBP) range is reached or maximum of 15mg/hour is achieved.	Labetalol is given intravenous bolus starting with 20mg over 2 minutes, which is repeated at 20, 40, or 80mg injections every 10 minutes until the target systolic blood pressure (SBP) range is reached or a maximum of 300mg is administered.
Overall Number of Participants Analyzed	109	115
Median (Inter-Quartile Range); Unit of Measure: hours
	4.6; (3.5 to 6.6)	4.6; (3.1 to 7.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nicardipine, Labetalol
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.76
	Comments	[Not Specified]
	Method	Wilcoxon (Mann-Whitney)
	Comments	[Not Specified]

4. Secondary Outcome

Title	Treatment Failure
Description	Treatment failure is defined as admission to the hospital or observation unit for BP management
Time Frame	6 hours

Outcome Measure Data

Analysis Population Description

these are the correct participant numbers for this secondary analysis

Arm/Group Title	Nicardipine	Labetalol
Arm/Group Description:	Nicardipine was administered at 5mg/hour and increased every 5 minutes by 2.5 mg/hour until the target systolic blood pressure (SBP) range is reached or maximum of 15mg/hour is achieved.	Labetalol is given intravenous bolus starting with 20mg over 2 minutes, which is repeated at 20, 40, or 80mg injections every 10 minutes until the target systolic blood pressure (SBP) range is reached or a maximum of 300mg is administered.
Overall Number of Participants Analyzed	109	115
Measure Type: Number; Unit of Measure: percentage of participants
	43.1	37.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nicardipine, Labetalol
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.38
	Comments	[Not Specified]
	Method	Chi-squared
	Comments	[Not Specified]

5. Secondary Outcome

Title	Subjects Requiring the Use of Intravenous Rescue Medications
Description	The percent of subjects requiring the use of intravenous rescue medications
Time Frame	6 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nicardipine	Labetalol
Arm/Group Description:	Nicardipine was administered at 5mg/hour and increased every 5 minutes by 2.5 mg/hour until the target systolic blood pressure (SBP) range is reached or maximum of 15mg/hour is achieved.	Labetalol is given intravenous bolus starting with 20mg over 2 minutes, which is repeated at 20, 40, or 80mg injections every 10 minutes until the target systolic blood pressure (SBP) range is reached or a maximum of 300mg is administered.
Overall Number of Participants Analyzed	110	116
Measure Type: Number; Unit of Measure: percentage of participants
	15.5	22.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nicardipine, Labetalol
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.18
	Comments	[Not Specified]
	Method	Chi-squared
	Comments	[Not Specified]

6. Secondary Outcome

Title	Transition Time to Oral Medication
Description	The median transition time (in hours) to oral medication
Time Frame	6 hours

Outcome Measure Data

Analysis Population Description

these are the correct participant numbers for this secondary analysis

Arm/Group Title	Nicardipine	Labetalol
Arm/Group Description:	Nicardipine was administered at 5mg/hour and increased every 5 minutes by 2.5 mg/hour until the target systolic blood pressure (SBP) range is reached or maximum of 15mg/hour is achieved.	Labetalol is given intravenous bolus starting with 20mg over 2 minutes, which is repeated at 20, 40, or 80mg injections every 10 minutes until the target systolic blood pressure (SBP) range is reached or a maximum of 300mg is administered.
Overall Number of Participants Analyzed	96	85
Median (Inter-Quartile Range); Unit of Measure: hours
	4.9; (1.4 to 10.9)	6.4; (2.2 to 16.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nicardipine, Labetalol
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.11
	Comments	[Not Specified]
	Method	Wilcoxon (Mann-Whitney)
	Comments	[Not Specified]

Adverse Events

Time Frame	Emergency Room visit
Adverse Event Reporting Description	Elevated cardiac markers
Arm/Group Title	Nicardipine		Labetalol
Arm/Group Description	Nicardipine dosing was 5 mg/hour		Bolus Labetalol began at 20 mg over 2 minutes
All-Cause Mortality
	Nicardipine		Labetalol
	Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--
Serious Adverse Events
	Nicardipine		Labetalol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/110 (0.00%)		0/116 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Nicardipine		Labetalol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/110 (0.91%)		0/116 (0.00%)
Cardiac disorders
Elevated cardiac biomarkers † 1	1/110 (0.91%)	1	0/116 (0.00%)	0
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA (10.0)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS 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.

Results Point of Contact

• Name/Title: Frank Peacock MD
• Organization: Cleveland Clinic
• Phone: (216) 445-4557
• EMail: peacocw@ccf.org

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: The Cleveland Clinic
• ClinicalTrials.gov Identifier: NCT00765648
• Other Study ID Numbers: 2008-001
• First Submitted: October 1, 2008
• First Posted: October 3, 2008
• Results First Submitted: July 18, 2011
• Results First Posted: December 11, 2014
• Last Update Posted: January 6, 2015