New Study Demonstrates Ready-to Use Cardene I.V. More Effective than Labetalol for Immediate Control of Blood Pressure in Emergency Room Patients

-- CLUE Data Presented During the 2010 American College of Emergency Physicians Research Forum --

BEDMINSTER, N.J.--(BUSINESS WIRE)--Sep 28, 2010 - Results from the CLUE study, a head-to-head comparison between Ready-to-Use Cardene® I.V. (nicardipine) and labetalol in the emergency room, showed that Ready-to-Use Cardene I.V. lowers acutely elevated blood pressure more effectively than labetalol. These data were presented today at the annual meeting of the American College of Emergency Physicians (ACEP) in Las Vegas, Nevada.

“The CLUE study is important for emergency room physicians because these findings demonstrate that using nicardipine instead of labetalol is more effective at controlling blood pressure in hypertensive patients,” says Frank Peacock, M.D. of the Cleveland Clinic, the study's lead investigator. "When physicians need to rapidly lower blood pressure, nicardipine is faster than labetalol. In this study, patients treated with nicardipine were approximately three times more likely to reach the target blood pressure range within 30 minutes than those treated with labetalol."

A sudden, sustained rise in blood pressure is abnormal and may cause irreversible damage to the kidneys, heart, brain, or other organs. The longer the blood pressure remains high, the greater the risk of organ damage. It is believed that a rapid, smooth reduction of the elevated blood pressure to a target range may improve patient outcomes.1-4

A variety of agents may be used to treat high blood pressure in an emergency room setting. However, there have been few randomized studies comparing the relative benefits and risks of different antihypertensives, and there is little standardization of treatment regimens. Consequently, the choice of which agent to use in a particular patient may be determined by convenience alone. Only recently has nicardipine become available in Ready-to-Use bags which can be kept at the point-of-care and immediately available to treat the patient presenting with a hypertensive emergency.

“It is important to provide physicians with evidence-based guidance regarding the safe and effective lowering of blood pressure into a predefined target range,” says Graham May, M.D., Chief Medical Officer for EKR Therapeutics, the company that developed and markets Ready-to-Use Cardene® I.V. “This is especially true in the emergency room where prompt control of high blood pressure may reduce the severity of a heart attack or stroke.”

About the CLUE Study5

Methods: Eligible patients had to have two systolic blood pressure (BP) readings >180 mmHg measured at least 10 minutes apart, and no contraindications to either nicardipine (NIC) or labetalol (LAB). Before randomization, the emergency room physician specified a desired target systolic BP for the patient. This pressure ± 20 mmHg was called the Target Systolic Blood Pressure Range (TSBPR). NIC was started at an infusion rate of 5 mg/hr, and titrated upwards every five minutes by 2.5 mg/hr until the TSBPR was achieved, or a maximum rate of 15 mg/hr was reached; once in the target range, the NIC infusion rate was decreased to 3 mg/hr. LAB was first administered as a 20 mg bolus over two minutes, with 20, 40, or 80 mg boluses repeated every 10 minutes until the TSBPR was achieved, or a maximum of 300 mg had been given. The active treatment phase of the study was 30 minutes.

Results: CLUE enrolled 226 patients, 52.7% female, 76.4% African American, with a mean age of 52.6±14.6 y. On admission, 143 (63.3%) patients (NIC 71, LAB 72) had symptoms or signs suggesting end organ damage. There were no significant between-treatment differences in mean entry systolic BP (213.4±21.8 mmHg), diastolic BP (116.8±17.97 mmHg), demographic characteristics, or laboratory parameters, except that NIC patients were more likely to be diabetic (34.4% vs. 21.7%, p=0.032), or have hyperlipidemia (43.4% vs. 27.9%, p=0.017), and there were more past smokers [67.2% vs. 49.1%, p=0.006] and current smokers [42.2% vs. 27.3%, p=0.018] in the LAB group.

110 patients were randomized to NIC, 116 to LAB. After 30 minutes, more NIC than LAB patients had achieved the TSBPR (91.7 vs. 82.5%, p=0.039). BP was recorded every five minutes during the study period (a total of 6 measures) and more NIC than LAB patients had 5 and 6 readings within the TSBPR (47.3% vs. 32.8%, p=0.026). Adverse events were rare in either treatment group. The mean heart rate in LAB patients was slower than in NIC patients at all time points after the start of treatment (p<0.01).

About Ready-to-Use Cardene® I.V.

Ready-to-Use Cardene® I.V. (nicardipine hydrochloride) is a premixed intravenous (IV) formulation of the calcium ion influx inhibitor indicated for the short-term treatment of hypertension when oral therapy is not feasible or desirable. Ready-to-Use Cardene I.V. is available as a single (0.1 mg/mL) or double (0.2 mg/mL) concentration of nicardipine, in either dextrose or saline, premixed in 200 mL intravenous bags.

Ready-to-Use Cardene I.V. provides practical advantages for hospitals, such as the convenience of point-of-use access in patient care areas. In addition to supporting The Joint Commission standards6 and American Society of Health-System Pharmacists guidelines7 for dispensing medication in the most ready to administer form, Ready-to-Use Cardene I.V. facilitates rapid intervention in emergency settings, eliminates point-of-care medication admixture errors, and is well suited to meet a hospital's after-pharmacy-hours medication needs.

Cardene I.V. Premixed Injection is contraindicated in patients with advanced aortic stenosis because part of the effect of Cardene I.V. is secondary to reduced afterload.

In administering nicardipine, close monitoring of blood pressure and heart rate is required. Nicardipine may occasionally produce symptomatic hypotension or tachycardia. Avoid systemic hypotension when administering the drug to patients who have sustained an acute cerebral infarction or hemorrhage.

Increases in frequency, duration, or severity of angina have been seen in chronic therapy with oral nicardipine. Induction or exacerbation of angina has been seen in less than 1% of coronary artery disease patients treated with Cardene I.V. The mechanism of this effect has not been established.

Titrate slowly when using Cardene I.V., particularly in combination with a beta-blocker, in patients with heart failure or significant left ventricular dysfunction because of possible negative inotropic effects.

Since nicardipine is metabolized in the liver, consider lower dosages and closely monitor responses in patients with impaired liver function or reduced hepatic blood flow.

When Cardene I.V. was given to mild to moderate hypertensive patients with moderate renal impairment, a significantly lower systemic clearance and higher area under the curve (AUC) was observed. These results are consistent with those seen after oral administration of nicardipine. Titrate gradually in patients with renal impairment.

To reduce the possibility of venous thrombosis, phlebitis, local irritation, swelling, extravasation, and the occurrence of vascular impairment, administer drug through large peripheral veins or central veins rather than arteries or small peripheral veins, such as those on the dorsum of the hand or wrist. To minimize the risk of peripheral venous irritation, change the site of the drug infusion every 12 hours.

Most common adverse reactions are headache (15%), hypotension (6%), nausea/vomiting (5%) and tachycardia (4%).

Full prescribing, safety, and additional information on Ready-to-Use Cardene I.V. is available at www.cardeneiv.com.

About EKR Therapeutics

Headquartered in Bedminster, New Jersey, EKR Therapeutics is a specialty pharmaceutical company focused on the acute-care hospital setting. EKR is committed to serving the needs of this important segment of the healthcare market by providing novel products offering broader therapeutic potential and superior patient outcomes. Founded in late 2005 by veteran healthcare and business executives, EKR has brought together a highly cohesive team of pharmaceutical professionals with established records of accomplishments in acute care. A privately held company, EKR has investment support from leading venture capital and private equity firms. For additional information about EKR, visit the company's website at www.ekrtx.com.

References:

1. Suri MF, Vazquez G, Ezzeddine MA, Qureshi AI. A multicenter comparison of outcomes associated with intravenous nitroprusside and nicardipine treatment among patients with intracerebral hemorrhage. Eurocrat Care. 2009;11(1):50-5.

2. Ahmed N, Dahlgren N, Brainin M, et al. Relationship of blood pressure, antihypertensive therapy, and outcome in ischemic stroke treated with intravenous thrombolysis: retrospective analysis from Safe Implementation of Thrombolysis in Stroke-International Stroke Thrombolysis Register (SITS-ISTR). Stroke. 2009;40(7):2442-9.

3. Anderson CS, Huang Y, Arima H, et al. Effects of early intensive blood pressure-lowering treatment on the growth of hematoma and perihematomal edema in acute intracerebral hemorrhage: the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT). Stroke. 2010;41(2):307-12.

4. Qureshi AI, Palesch YY, Martin R, et al. Effect of systolic blood pressure reduction on hematoma expansion, perihematomal edema, and 3-month outcome among patients with intracerebral hemorrhage: results from the antihypertensive treatment of acute cerebral hemorrhage study. Arch Neurol. 2010 ;67(5):570-6.

5. Peacock W, Baumann B, Borczuk P, et al. CLUE: A comparative effectiveness trial of nicardipine versus labetalol use in the emergency department. Ann Emerg Med. 2010;56(3):S34-35. Abstract 103.

6. Rich DS. New JCAHO medication management standards for 2004. Am J Health-Syst Pharm. 2004;61(13): 1349-1358.

7. American Society of Health-System Pharmacists. ASHP guidelines; minimum standard for pharmacies in hospitals. Am J Health-Syst Pharm. 2007;64 (19):2711-2717.

Contact: EKR Therapeutics
Doug Petkus, 609-923-2838

 

Posted: September 2010

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