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Comparison of AQUAVAN® Injection to DISOPRIVAN® Injectable Emulsion for Anesthesia During Coronary Artery Surgery

Primary Purpose

Ischemic Coronary Artery Disease, Coronary Artery Bypass Surgery

Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
fospropofol
propofol
Sponsored by
Eisai Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ischemic Coronary Artery Disease focused on measuring Coronary Artery Bypass Surgery, AQUAVAN® Injection, DISOPRIVAN® Injectable Emulsion., ischemic coronary artery disease

Eligibility Criteria

21 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Patients were between the ages of 21 and 70 years, inclusive. Patients were scheduled for first-time elective coronary artery bypass graft surgery, with 1 to 4 grafts planned. Patients had an American Society of Anesthesiologists (ASA) Physical Classification System status of II or III. Patients had a "good" left ventricular function as defined by a cardiac ejection fraction >=50% measured by cardiac catheterization or other quantitative technique. Patients provided written Informed Consent after receiving a full explanation of the extent and nature of the study and were willing to comply with the study procedures. Patients, if female, were surgically sterile or postmenopausal. Exclusion Criteria: Patient had prior coronary bypass grafting or other cardiac surgery. Patient had uncontrolled hypertension (diastolic >110 mm Hg) or required additional intervention while hospitalized prior to surgery to control blood pressure. Patient had a medical history of renal disease or creatinine >1.4 mg/dL. Patient had known hemodynamically significant valvular abnormalities, except Grade 1 tricuspid or mitral insufficiency. Patient had severe obesity, defined as a body mass index (BMI) >35. Patient failed the Allen's Test to confirm the patency of the ulnar artery. Patient had severe or uncontrolled systemic illness (e.g., pulmonary disease, cancer, endocrine abnormalities). Patient had insulin-dependent diabetes. Patient had a history of stroke or current neurological disease (e.g., dementia, neuropathy), as determined by the Investigator. Patient had anticipated difficulties with intubation, in the judgment of the Investigator. Patient had a history of alcohol abuse, as determined by the Investigator; Patient had participated in an investigational drug study within 1 month prior to study start. Patient had donated >300 mL of blood within 1 month prior to study start. Patient had a positive medical history for drug abuse. Patient had a known infection with human immunodeficiency virus (HIV), Hepatitis B, and/or Hepatitis C. Patient had any history of anxiety or psychiatric illness or was currently using antidepressants, monoamine oxidase (MAO) inhibitors, anti-anxiety medications or other drugs with central nervous system (CNS) effects prior to their preoperative hospital stay. Patient had uncorrected visual problems, including cataracts, glaucoma, or any significant abnormalities found on fundoscopic examination that would interfere with visual assessment of drug safety. Patient had any history of adverse reaction to any opiate or anesthetic agent. Patient, if male, did not agree to use an effective method of birth control between the time of screening and end of study.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Active Comparator

    Arm Label

    fospropofol

    propofol

    Arm Description

    Outcomes

    Primary Outcome Measures

    Median time (minutes) to loss of consciousness from induction start (reported as median and range).

    Secondary Outcome Measures

    Median time (minutes) to induction from start of infusion (reported as median and range).
    Time (minutes) to intubation from induction start (reported as median and range).
    Time (minutes) to extubation from end of infusion (reported as median and range).
    Time (minutes) to last suture from induction start (reported as median and range).
    Time (minutes) to full awareness from end of infusion (reported as median and range).
    Median time from End of Infusion to First Modified Ramsey Score of 3 (reported as median and range).

    Full Information

    First Posted
    September 13, 2005
    Last Updated
    June 10, 2010
    Sponsor
    Eisai Inc.
    Collaborators
    PPD
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00209521
    Brief Title
    Comparison of AQUAVAN® Injection to DISOPRIVAN® Injectable Emulsion for Anesthesia During Coronary Artery Surgery
    Official Title
    Phase 2, Randomized Study of AQUAVAN® Injection In Elective Coronary Artery Surgery With Comparison to DISOPRIVAN® Injectable Emulsion
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    June 2010
    Overall Recruitment Status
    Completed
    Study Start Date
    June 2002 (undefined)
    Primary Completion Date
    July 2003 (Actual)
    Study Completion Date
    July 2003 (Actual)

    3. Sponsor/Collaborators

    Name of the Sponsor
    Eisai Inc.
    Collaborators
    PPD

    4. Oversight

    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    This is an exploratory clinical trial designed to examine the efficacy, safety and tolerability of fospropofol (AQUAVAN) Injection compared to propofol (DISOPRIVAN) Injectable Emulsion when used to preoperatively sedate, induce, and maintain general anesthesia and to postoperatively sedate patients undergoing elective coronary artery surgery.
    Detailed Description
    This Phase 2, open-label, single-center, randomized clinical trial was designed to examine the efficacy and tolerability of AQUAVAN® Injection (hereafter, referred to as AQUAVAN) when used to preoperatively sedate, induce, and maintain general anesthesia and to postoperatively sedate patients undergoing elective coronary artery surgery. Eligible patients were randomized to either AQUAVAN or DISOPRIVAN® Injectable Emulsion (hereafter, referred to as DISOPRIVAN) following screening and prior to their arrival in the surgical suite. On the day of surgery, after the administration a 0.5 mg/kg bolus dose of lignocaine, preoperative sedation began using the target-controlled infusion (TCI) system to target desired sedation plasma concentrations of either AQUAVAN or DISOPRIVAN, depending on the randomization schedule. The Bispectral (BIS) Index was used to guide study drug administration; target BIS ranges were 60 to 80 for sedation and 40 to 60 for the maintenance of anesthesia. Adequate sedative/hypnotic effect during surgical anesthesia was characterized by the portion of time within the target BIS Index range versus total surgical time. Following this, during postsurgical sedation, inadequate sedative/hypnotic effect was characterized by the number, duration, and magnitude of BIS scores outside of the target range versus total postsurgical sedation time. During postsurgical sedation, the Modified Ramsey Scale was used as an additional clinical tool to evaluate the state of sedation, with an attempt to maintain the score between 3 and 5. The overall quality of induction, maintenance and ease of control of anesthesia, and quality of sedation before and during cardiopulmonary bypass (CPB), were each graded by the anesthesiologist. Continuous monitoring of blood pressure and heart rate were used to assess the hemodynamic effect of study drug. Hypertension and hypotension were defined as excursions of >/= 20% from the baseline value.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Ischemic Coronary Artery Disease, Coronary Artery Bypass Surgery
    Keywords
    Coronary Artery Bypass Surgery, AQUAVAN® Injection, DISOPRIVAN® Injectable Emulsion., ischemic coronary artery disease

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    16 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    fospropofol
    Arm Type
    Experimental
    Arm Title
    propofol
    Arm Type
    Active Comparator
    Intervention Type
    Drug
    Intervention Name(s)
    fospropofol
    Other Intervention Name(s)
    fospropofol disodium, LUSEDRA, E2083, GPI-15715, AQUAVAN
    Intervention Description
    Using a Target Controlled Infusion (TCI) system, the target plasma concentrations of propofol to be administered from AQUAVAN were 0.7 μg/mL (sedation) and 2.5 μg/mL (maintain anesthesia).
    Intervention Type
    Drug
    Intervention Name(s)
    propofol
    Other Intervention Name(s)
    Disoprivan, propofol injectable emulsion
    Intervention Description
    Using a Target Controlled Infusion (TCI) system, the target plasma concentrations of propofol to be administered from Disoprivan were 1.0 μg/mL (sedation) and 3.0 μg/mL (maintain anesthesia).
    Primary Outcome Measure Information:
    Title
    Median time (minutes) to loss of consciousness from induction start (reported as median and range).
    Time Frame
    Day 1
    Secondary Outcome Measure Information:
    Title
    Median time (minutes) to induction from start of infusion (reported as median and range).
    Time Frame
    Day 1
    Title
    Time (minutes) to intubation from induction start (reported as median and range).
    Time Frame
    Day 1
    Title
    Time (minutes) to extubation from end of infusion (reported as median and range).
    Time Frame
    Day 1
    Title
    Time (minutes) to last suture from induction start (reported as median and range).
    Time Frame
    Day 1
    Title
    Time (minutes) to full awareness from end of infusion (reported as median and range).
    Time Frame
    Day 1
    Title
    Median time from End of Infusion to First Modified Ramsey Score of 3 (reported as median and range).
    Time Frame
    Day 1

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    21 Years
    Maximum Age & Unit of Time
    70 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Patients were between the ages of 21 and 70 years, inclusive. Patients were scheduled for first-time elective coronary artery bypass graft surgery, with 1 to 4 grafts planned. Patients had an American Society of Anesthesiologists (ASA) Physical Classification System status of II or III. Patients had a "good" left ventricular function as defined by a cardiac ejection fraction >=50% measured by cardiac catheterization or other quantitative technique. Patients provided written Informed Consent after receiving a full explanation of the extent and nature of the study and were willing to comply with the study procedures. Patients, if female, were surgically sterile or postmenopausal. Exclusion Criteria: Patient had prior coronary bypass grafting or other cardiac surgery. Patient had uncontrolled hypertension (diastolic >110 mm Hg) or required additional intervention while hospitalized prior to surgery to control blood pressure. Patient had a medical history of renal disease or creatinine >1.4 mg/dL. Patient had known hemodynamically significant valvular abnormalities, except Grade 1 tricuspid or mitral insufficiency. Patient had severe obesity, defined as a body mass index (BMI) >35. Patient failed the Allen's Test to confirm the patency of the ulnar artery. Patient had severe or uncontrolled systemic illness (e.g., pulmonary disease, cancer, endocrine abnormalities). Patient had insulin-dependent diabetes. Patient had a history of stroke or current neurological disease (e.g., dementia, neuropathy), as determined by the Investigator. Patient had anticipated difficulties with intubation, in the judgment of the Investigator. Patient had a history of alcohol abuse, as determined by the Investigator; Patient had participated in an investigational drug study within 1 month prior to study start. Patient had donated >300 mL of blood within 1 month prior to study start. Patient had a positive medical history for drug abuse. Patient had a known infection with human immunodeficiency virus (HIV), Hepatitis B, and/or Hepatitis C. Patient had any history of anxiety or psychiatric illness or was currently using antidepressants, monoamine oxidase (MAO) inhibitors, anti-anxiety medications or other drugs with central nervous system (CNS) effects prior to their preoperative hospital stay. Patient had uncorrected visual problems, including cataracts, glaucoma, or any significant abnormalities found on fundoscopic examination that would interfere with visual assessment of drug safety. Patient had any history of adverse reaction to any opiate or anesthetic agent. Patient, if male, did not agree to use an effective method of birth control between the time of screening and end of study.
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    James Vornov, PhD,MD
    Organizational Affiliation
    Eisai Inc.
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Learn more about this trial

    Comparison of AQUAVAN® Injection to DISOPRIVAN® Injectable Emulsion for Anesthesia During Coronary Artery Surgery

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