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Study of Clevidipine Assessing Its Postoperative Antihypertensive Effect in Cardiac Surgery (ESCAPE-2)

Phase 3
Completed
Conditions
Hypertension
Interventions
Drug: placebo
Registration Number
NCT00093262
Lead Sponsor
The Medicines Company
Brief Summary

The purpose of this study is to establish the efficacy of of clevidipine versus placebo in treating postoperative hypertension. Approximately 100 patients with postoperative hypertension undergoing coronary artery bypass grafting (CABG), off-pump coronary artery bypass (OPCAB) or minimally invasive direct coronary artery bypass (MIDCAB) surgery and/or valve replacement/repair procedures were anticipated to be randomly assigned to one of two treatment groups: clevidipine or placebo.

Detailed Description

The primary objective was to determine the efficacy of clevidipine versus placebo in treating postoperative hypertension by comparing the incidence of bailout in the clevidipine and placebo treatment groups during the 30-minute time period from initiation of study drug. Secondary objectives included assessments of efficacy through measuring time to target blood pressure (BP) lowering effect defined as 15% reduction in SBP, change in mean arterial pressure (MAP) and the incidence of bailout by causality. Assessments for safety included change in heart rate (HR) from baseline.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
206
Inclusion Criteria
  • Provide written informed consent before initiation of any study-related procedures.
  • Be at least 18 years of age
  • Be scheduled for cardiac surgery (including Coronary Artery Bypass Grafting [CABG], Off Pump Coronary Artery Bypass [OPCAB], Minimally Invasive Direct Coronary Artery Bypass [MIDCAB] surgery, and/or valve replacement/repair procedures)

Pre-randomization

Exclusion Criteria
  • Women of child-bearing potential (unless they have a negative pregnancy test)
  • Recent cerebrovascular accident (within 3 months before randomization)
  • Known intolerance to calcium channel blockers
  • Allergy to soybean oil or egg lecithin (components of the lipid vehicle)
  • Pre-existing left bundle branch block or permanent ventricular pacing
  • Any other disease or condition, which, in the judgment of the investigator would place a patient at undue risk by being enrolled in the trial.
  • Participation in another therapeutic drug or therapeutic device trial within 30 days of starting study

Post-randomization Inclusion Criteria:

  • Expected to survive beyond 24 hours post-surgical procedure
  • No surgical complications or conditions, present or anticipated, that preclude them from inclusion in a double blind, placebo-controlled study
  • Determined to be hypertensive (SBP > 140 mm Hg) within 4 hours of arrival in a postoperative setting
  • It is the investigator's intent to lower the patient's SBP by a minimum of 15% from its baseline value

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
placeboplaceboPlacebo consisted of 20% lipid emulsion (the same lipid vehicle used for clevidipine) administered in a blinded fashion intravenously following the same study drug administration guidelines as with clevidipine study drug administration guidelines. As with clevidipine, placebo was to be administered for a minimum of 30 minutes, unless bailout occurred, and up to a maximum of one hour.
clevidipineclevidipineClevidipine was administered in a blinded fashion intravenously, starting with an infusion rate of 0.4 μg/kg/min (non weight-based equivalent is 2 mg/hr), titrating upward, as tolerated by the patient, in doubling increments approximately every 90 seconds up to an infusion rate of 3.2 μg/kg/min (16 mg/hr) to achieve the desired blood pressure-lowering effect. Up-titration to infusion rates above 3.2 μg/kg/min could be used, guided by the patient's response, by increasing the infusion rate in serial increments of 1.5 μg/kg/min, up to the maximum recommended clevidipine infusion rate of 8.0 μg/kg/min. Clevidipine was to be administered for a minimum of 30 minutes, unless bailout occurred, and up to a maximum of one hour.
Primary Outcome Measures
NameTimeMethod
Incidence of bailout during 30-minute treatment periodDuring the first 30 minutes post study drug initiation

The incidence of bailout defined as the premature and permanent discontinuation of study drug categorized according to the following reasons:

* Bailout for lack of efficacy

* Bailout for safety reason(s)

* Bailout due to treatment failure

Secondary Outcome Measures
NameTimeMethod
Incidence of bailout by causalityDuring the first 30 minutes post study drug initiation
Median time to target SBP lowering effect (defined as a reduction by 15% or more)During the first 30 minutes post study drug initiation
Mean arterial pressure (MAP) change from baselineDuring the first 30 minutes post study drug initiation
Heart rate change from baselineDuring the first 30 minutes post study drug initiation

Trial Locations

Locations (15)

Keck School of Medicine, University of Southern California

🇺🇸

Los Angeles, California, United States

Emory Hospital

🇺🇸

Atlanta, Georgia, United States

International Heart Institute

🇺🇸

Missoula, Montana, United States

Discovery Alliance - Methodist Hospital / Diagnostic West Pavillion

🇺🇸

Houston, Texas, United States

Discovery Alliance - Mobile Infirmary Medical Center

🇺🇸

Mobile, Alabama, United States

Huntington Memorial Hospital

🇺🇸

Pasadena, California, United States

Stanford University School of Medicine

🇺🇸

Stanford, California, United States

Wesley Medical Center

🇺🇸

Wichita, Kansas, United States

Heart Care Research Foundation

🇺🇸

Blue Island, Illinois, United States

Columbia University - College of Physicians and Surgeons

🇺🇸

New York, New York, United States

St. Lukes Hospital

🇺🇸

Kansas City, Missouri, United States

Mt. Sinai Medical Center

🇺🇸

New York, New York, United States

Carolinas Medical Center

🇺🇸

Charlotte, North Carolina, United States

Medical College of Wisconsin VAMC - Milwaukee

🇺🇸

Milwaukee, Wisconsin, United States

MacNeal Hospital

🇺🇸

Glencoe, Illinois, United States

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