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Study of Clevidipine Assessing Its Preoperative Antihypertensive Effect in Cardiac Surgery (ESCAPE-1)

Phase 3
Completed
Conditions
Hypertension
Interventions
Drug: placebo
Registration Number
NCT00093249
Lead Sponsor
The Medicines Company
Brief Summary

The purpose of this study is to determine the efficacy of clevidipine injection versus placebo in treating preoperative hypertension.

Detailed Description

Initiation of study drug infusion will commence with the occurrence of protocol-defined preoperative hypertension (SBP \> 160 mmHg) as measured via an indwelling arterial line.

The study drug (clevidipine or placebo) may be administered to treat hypertension until one hour has elapsed, or until induction of anesthesia, whichever occurs first.

The primary endpoint of bailout described (as defined per protocol) as bailout for lack of efficacy, bailout for safety reason or bailout due to treatment failure will be determined during the 30-minute period from study drug initiation.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
105
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)
  • Have a recent history (within 6 months of randomization) of hypertension requiring treatment with antihypertensive medication(s) or be actively hypertensive upon admission

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:

  • After the insertion of an arterial line, the patient is determined to meet the per protocol preoperative definition of hypertension, i.e. systolic blood pressure (SBP) > 160 mmHg
  • 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 by intravenous (IV) infusion, starting at a rate of 0.4 μg/kg/min (non weight-based equivalent is 2 mg/hr) and titrating upward, as tolerated, in doubling increments approximately every 90 seconds to achieve the desired blood pressure-lowering effect. Up-titration to 3.2 μg/kg/min (16 mg/hr) was allowed. Infusion rates above 3.2 μg/kg/min could be used, guided by the patient's response, by increasing 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

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
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
Incidence of bailout by causalityDuring the first 30 minutes post study drug initiation

Trial Locations

Locations (12)

Cardio-Thoracic Surgeons, PC

🇺🇸

Birmingham, Alabama, United States

St Vincent Medical Center

🇺🇸

Los Angeles, California, United States

Memorial Herman Memorial City Hospital

🇺🇸

Houston, Texas, United States

Texas Heart Institute

🇺🇸

Houston, Texas, United States

Swedish Hospital Medical Center

🇺🇸

Seattle, Washington, United States

Discovery Alliance - Hudson

🇺🇸

Hudson, Florida, United States

Discovery Alliance - Sacred Heart Hospital

🇺🇸

Pensacola, Florida, United States

Atlanta VA Medical Center

🇺🇸

Atlanta, Georgia, United States

MacNeal Hospital

🇺🇸

Berwyn, Illinois, United States

The Christ Hospital, The Linder Clinical Trial Center

🇺🇸

Cincinnati, Ohio, United States

Wake Forest University School of Medicine

🇺🇸

Winston-Salem, North Carolina, United States

Houston Northwest Medical Center

🇺🇸

Houston, Texas, United States

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