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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
The Medicines Company
ClinicalTrials.gov Identifier:
NCT00093249
First received: October 5, 2004
Last updated: August 21, 2014
Last verified: August 2014
  Purpose

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


Condition Intervention Phase
Hypertension
Drug: clevidipine
Drug: placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: Efficacy Study of Clevidipine Assessing Its Preoperative Antihypertensive Effect in Cardiac Surgery (ESCAPE-1)

Resource links provided by NLM:


Further study details as provided by The Medicines Company:

Primary Outcome Measures:
  • Incidence of bailout during 30-minute treatment period [ Time Frame: During the first 30 minutes post study drug initiation ] [ Designated as safety issue: No ]

    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:
  • 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 ] [ Designated as safety issue: No ]
  • Mean arterial pressure (MAP) change from baseline [ Time Frame: During the first 30 minutes post study drug initiation ] [ Designated as safety issue: No ]
  • Heart rate change from baseline [ Time Frame: During the first 30 minutes post study drug initiation ] [ Designated as safety issue: No ]
  • Incidence of bailout by causality [ Time Frame: During the first 30 minutes post study drug initiation ] [ Designated as safety issue: No ]

Enrollment: 105
Study Start Date: January 2004
Study Completion Date: November 2004
Primary Completion Date: November 2004 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00093249

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:
Responsible Party: The Medicines Company
ClinicalTrials.gov Identifier: NCT00093249     History of Changes
Other Study ID Numbers: TMC-CLV-03-01, ESCAPE-1
Study First Received: October 5, 2004
Last Updated: August 21, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by The Medicines Company:
Pre-operative hypertension

Additional relevant MeSH terms:
Hypertension
Cardiovascular Diseases
Vascular Diseases
Antihypertensive Agents
Clevidipine
Calcium Channel Blockers
Cardiovascular Agents
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014