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

Tracking Information

• First Submitted Date: October 5, 2004
• First Posted Date: October 7, 2004
• Last Update Posted Date: August 22, 2014
• Study Start Date: January 2004
• Actual Primary Completion Date: November 2004 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 5, 2014)

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

• Original Primary Outcome Measures: Not Provided

Current Secondary Outcome Measures (submitted: May 5, 2014)

• 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 ]
• Mean arterial pressure (MAP) change from baseline [ Time Frame: During the first 30 minutes post study drug initiation ]
• Heart rate change from baseline [ Time Frame: During the first 30 minutes post study drug initiation ]
• Incidence of bailout by causality [ Time Frame: During the first 30 minutes post study drug initiation ]

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of Clevidipine Assessing Its Preoperative Antihypertensive Effect in Cardiac Surgery (ESCAPE-1)
• Official Title: Efficacy Study of Clevidipine Assessing Its Preoperative Antihypertensive Effect in Cardiac Surgery (ESCAPE-1)
• 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.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double; Primary Purpose: Treatment
• Condition: Hypertension

Intervention

• 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
• Drug: placebo
  Placebo (20% lipid emulsion - vehicle) will be administered intravenously in a fashion identical to clevidipine as described above.

Study Arms

• 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.
  Intervention: Drug: clevidipine
• 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.
  Intervention: Drug: placebo

• Publications *: 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 8, 2012): 105
• Original Enrollment (submitted: June 23, 2005): 100
• Actual Study Completion Date: November 2004
• Actual Primary Completion Date: November 2004 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00093249
• Other Study ID Numbers: TMC-CLV-03-01; ESCAPE-1 ( Other Identifier: Sponsor )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: The Medicines Company
• Original Responsible Party: Not Provided
• Current Study Sponsor: The Medicines Company
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: The Medicines Company
• Verification Date: August 2014