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

• ClinicalTrials.gov Identifier: NCT00093262
• Recruitment Status: Completed
• First Posted: October 7, 2004
• Last Update Posted: May 8, 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: May 8, 2014
• Study Start Date: December 2003
• Actual Primary Completion Date: October 2004 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 6, 2014)

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

• Original Primary Outcome Measures: Not Provided

Current Secondary Outcome Measures (submitted: May 6, 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 Postoperative Antihypertensive Effect in Cardiac Surgery (ESCAPE-2)
• Official Title: Efficacy Study of Clevidipine Assessing Its Postoperative Antihypertensive Effect in Cardiac Surgery (ESCAPE-2)
• 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.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Hypertension

Intervention

• Drug: clevidipine
  Other Name: clevidipine, Cleviprex
• Drug: placebo

Study Arms

• Experimental: clevidipine
  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.
  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 *: Singla N, Warltier DC, Gandhi SD, Lumb PD, Sladen RN, Aronson S, Newman MF, Corwin HL; ESCAPE-2 Study Group. Treatment of acute postoperative hypertension in cardiac surgery patients: an efficacy study of clevidipine assessing its postoperative antihypertensive effect in cardiac surgery-2 (ESCAPE-2), a randomized, double-blind, placebo-controlled trial. Anesth Analg. 2008 Jul;107(1):59-67. doi: 10.1213/ane.0b013e3181732e53.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 6, 2014): 206
• Original Enrollment (submitted: June 23, 2005): 100
• Actual Study Completion Date: October 2004
• Actual Primary Completion Date: October 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)

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

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: NCT00093262
• Other Study ID Numbers: TMC-CLV-03-02; ESCAPE-2
• 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: May 2014