Hypertensive Urgency
Conditions
Keywords
hypertension, emergency department, Nicardipine, Labetalol, hypertensive emergency, hypertensive urgency
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.
Interventions
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
DRUGLabetalol
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.
Sponsors
EKR Therapeutics, Inc
The Cleveland Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects Achieving a Pre-defined Target Systolic Blood Pressure (BP) Within 30 Minutes. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Average Number of Dose Titrations Within 30 Minutes | 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 | 6 hours | Median number of hours from hospital admission until Emergency Department(ED)disposition |
| Treatment Failure | 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 | 6 hours | The percent of subjects requiring the use of intravenous rescue medications |
| Transition Time to Oral Medication | 6 hours | The median transition time (in hours) to oral medication |
Countries
United States
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.
Participants by arm
| Arm | Count |
|---|---|
| Nicardipine Dosing Was 5 mg/Hour nicardipine intravenous | 110 |
| Bolus Labetalol Began at 20 mg Over 2 Minutes Labetalol | 116 |
| Total | 226 |
Baseline characteristics
| Characteristic | Nicardipine Dosing Was 5 mg/Hour | Bolus Labetalol Began at 20 mg Over 2 Minutes | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 29 Participants | 18 Participants | 47 Participants |
| Age, Categorical Between 18 and 65 years | 81 Participants | 98 Participants | 179 Participants |
| Region of Enrollment United States | 110 participants | 116 participants | 226 participants |
| Sex: Female, Male Female | 60 Participants | 59 Participants | 119 Participants |
| Sex: Female, Male Male | 50 Participants | 57 Participants | 107 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 110 | 0 / 116 |
| serious Total, serious adverse events | 0 / 110 | 0 / 116 |
Outcome results
Primary
Percentage of Subjects Achieving a Pre-defined Target Systolic Blood Pressure (BP) Within 30 Minutes.
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
Population: Intent to treat cohort.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nicardipine | Percentage of Subjects Achieving a Pre-defined Target Systolic Blood Pressure (BP) Within 30 Minutes. | 91.7 percentage of participants |
| Labetalol | Percentage of Subjects Achieving a Pre-defined Target Systolic Blood Pressure (BP) Within 30 Minutes. | 82.5 percentage of participants |
p-value: 0.0495% CI: [-18, -0.6]Chi-squared
Secondary
Average Number of Dose Titrations Within 30 Minutes
Calculated as the mean (± standard deviation) number of titrations over 30 minutes for each treatment group
Time frame: 30 minutes
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nicardipine | Average Number of Dose Titrations Within 30 Minutes | 2.2 number of titrations | Standard Deviation 1 |
| Labetalol | Average Number of Dose Titrations Within 30 Minutes | 1.3 number of titrations | Standard Deviation 0.97 |
p-value: <0.001t-test, 2 sided
Secondary
Emergency Department(ED)Time to Disposition Decision
Median number of hours from hospital admission until Emergency Department(ED)disposition
Time frame: 6 hours
Population: these are the correct participant numbers for this secondary analysis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nicardipine | Emergency Department(ED)Time to Disposition Decision | 4.6 hours |
| Labetalol | Emergency Department(ED)Time to Disposition Decision | 4.6 hours |
p-value: 0.76Wilcoxon (Mann-Whitney)
Secondary
Subjects Requiring the Use of Intravenous Rescue Medications
The percent of subjects requiring the use of intravenous rescue medications
Time frame: 6 hours
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nicardipine | Subjects Requiring the Use of Intravenous Rescue Medications | 15.5 percentage of participants |
| Labetalol | Subjects Requiring the Use of Intravenous Rescue Medications | 22.4 percentage of participants |
p-value: 0.18Chi-squared
Secondary
Transition Time to Oral Medication
The median transition time (in hours) to oral medication
Time frame: 6 hours
Population: these are the correct participant numbers for this secondary analysis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nicardipine | Transition Time to Oral Medication | 4.9 hours |
| Labetalol | Transition Time to Oral Medication | 6.4 hours |
p-value: 0.11Wilcoxon (Mann-Whitney)
Secondary
Treatment Failure
Treatment failure is defined as admission to the hospital or observation unit for BP management
Time frame: 6 hours
Population: these are the correct participant numbers for this secondary analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nicardipine | Treatment Failure | 43.1 percentage of participants |
| Labetalol | Treatment Failure | 37.4 percentage of participants |
p-value: 0.38Chi-squared