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

• ClinicalTrials.gov Identifier: NCT00093249
• Recruitment Status: Completed
• First Posted: October 7, 2004
• Last Update Posted: August 22, 2014
• Sponsor: The Medicines Company
• Information provided by (Responsible Party): The Medicines Company

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Hypertension	Drug: clevidipine; Drug: placebo	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 105 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double
• Primary Purpose: Treatment
• Official Title: Efficacy Study of Clevidipine Assessing Its Preoperative Antihypertensive Effect in Cardiac Surgery (ESCAPE-1)
• Study Start Date: January 2004
• Actual Primary Completion Date: November 2004
• Actual Study Completion Date: November 2004

Arms and Interventions

Arm	Intervention/treatment
Experimental: clevidipine; Clevidipine 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.	Drug: clevidipine; Clevidipine (0.5 mg/mL in 20% lipid emulsion)will be administered intravenously at an initial infusion rate of 0.4 µg/kg/min and will be titrated, as tolerated, at the discretion of the investigator, in doubling increments approximately every 90 seconds up to a maximum of 3.2 µg/kg/min, in order to achieve the desired blood pressure lowering effect. Clevidipine may be titrated upwards or downwards and may be temporarily interrupted and restarted to attain the desired blood pressure effect. The maximum study drug infusion rate of 8.0 µg/kg/min may not be exceeded.; Other Name: clevidipine, Cleviprex
Placebo Comparator: placebo; 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; Placebo (20% lipid emulsion - vehicle) will be administered intravenously in a fashion identical to clevidipine as described above.

Outcome Measures

Primary Outcome Measures :

1. Incidence of bailout during 30-minute treatment period [ Time Frame: During 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 :

1. Median time to target SBP lowering effect (defined as a reduction by 15% or more) [ Time Frame: During the first 30 minutes post study drug initiation ]
2. Mean arterial pressure (MAP) change from baseline [ Time Frame: During the first 30 minutes post study drug initiation ]
3. Heart rate change from baseline [ Time Frame: During the first 30 minutes post study drug initiation ]
4. Incidence of bailout by causality [ Time Frame: During the first 30 minutes post study drug initiation ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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)
• 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

Contacts and Locations

Locations

United States, Alabama

Cardio-Thoracic Surgeons, PC

Birmingham, Alabama, United States, 35213

United States, California

St Vincent Medical Center

Los Angeles, California, United States, 90057

United States, Florida

Discovery Alliance - Hudson

Hudson, Florida, United States, 34667

Discovery Alliance - Sacred Heart Hospital

Pensacola, Florida, United States, 32503

United States, Georgia

Atlanta VA Medical Center

Atlanta, Georgia, United States, 30322

United States, Illinois

MacNeal Hospital

Berwyn, Illinois, United States, 60402

United States, North Carolina

Wake Forest University School of Medicine

Winston-Salem, North Carolina, United States, 27157

United States, Ohio

The Christ Hospital, The Linder Clinical Trial Center

Cincinnati, Ohio, United States, 45219

United States, Texas

Memorial Herman Memorial City Hospital

Houston, Texas, United States, 77024

Texas Heart Institute

Houston, Texas, United States, 77030

Houston Northwest Medical Center

Houston, Texas, United States, 77090

United States, Washington

Swedish Hospital Medical Center

Seattle, Washington, United States, 98104-1318

Sponsors and Collaborators

The Medicines Company

More Information

Publications of Results:

Levy JH, Mancao MY, Gitter R, Kereiakes DJ, Grigore AM, Aronson S, Newman MF. Clevidipine effectively and rapidly controls blood pressure preoperatively in cardiac surgery patients: the results of the randomized, placebo-controlled efficacy study of clevidipine assessing its preoperative antihypertensive effect in cardiac surgery-1. Anesth Analg. 2007 Oct;105(4):918-25, table of contents. doi: 10.1213/01.ane.0000281443.13712.b9.

• Responsible Party: The Medicines Company
• ClinicalTrials.gov Identifier: NCT00093249
• Other Study ID Numbers: TMC-CLV-03-01; ESCAPE-1 ( Other Identifier: Sponsor )
• First Posted: October 7, 2004
• Last Update Posted: August 22, 2014
• Last Verified: August 2014

Keywords provided by The Medicines Company:

Pre-operative hypertension

Additional relevant MeSH terms:

Hypertension; Vascular Diseases; Cardiovascular Diseases; Clevidipine; Calcium Channel Blockers; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Calcium-Regulating Hormones and Agents; Physiological Effects of Drugs