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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Hypertension

Intervention / Treatment
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* Drug: clevidipine
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Pre-randomization 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: clevidipine<br>Clevidipine 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. | Drug: clevidipine<br> <br> * Other names: clevidipine, Cleviprex;|
| Placebo Comparator: placebo<br>Placebo 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. | Drug: placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of bailout during 30-minute treatment period | 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 | During the first 30 minutes post study drug initiation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 baseline |  | During the first 30 minutes post study drug initiation | 
| Heart rate change from baseline |  | During the first 30 minutes post study drug initiation | 
| Incidence of bailout by causality |  | During the first 30 minutes post study drug initiation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Postoperative Hypertension