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

June 10, 2010 updated by: Eisai Inc.

Phase 2, Randomized Study of AQUAVAN® Injection In Elective Coronary Artery Surgery With Comparison to DISOPRIVAN® Injectable Emulsion

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.

Study Overview

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.

Study Type

Interventional

Enrollment (Actual)

16

Phase

  • Phase 2

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years to 70 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Patients were between the ages of 21 and 70 years, inclusive.
  2. Patients were scheduled for first-time elective coronary artery bypass graft surgery, with 1 to 4 grafts planned.
  3. Patients had an American Society of Anesthesiologists (ASA) Physical Classification System status of II or III.
  4. Patients had a "good" left ventricular function as defined by a cardiac ejection fraction >=50% measured by cardiac catheterization or other quantitative technique.
  5. 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.
  6. Patients, if female, were surgically sterile or postmenopausal.

Exclusion Criteria:

  1. Patient had prior coronary bypass grafting or other cardiac surgery.
  2. Patient had uncontrolled hypertension (diastolic >110 mm Hg) or required additional intervention while hospitalized prior to surgery to control blood pressure.
  3. Patient had a medical history of renal disease or creatinine >1.4 mg/dL.
  4. Patient had known hemodynamically significant valvular abnormalities, except Grade 1 tricuspid or mitral insufficiency.
  5. Patient had severe obesity, defined as a body mass index (BMI) >35.
  6. Patient failed the Allen's Test to confirm the patency of the ulnar artery.
  7. Patient had severe or uncontrolled systemic illness (e.g., pulmonary disease, cancer, endocrine abnormalities).
  8. Patient had insulin-dependent diabetes.
  9. Patient had a history of stroke or current neurological disease (e.g., dementia, neuropathy), as determined by the Investigator.
  10. Patient had anticipated difficulties with intubation, in the judgment of the Investigator.
  11. Patient had a history of alcohol abuse, as determined by the Investigator;
  12. Patient had participated in an investigational drug study within 1 month prior to study start.
  13. Patient had donated >300 mL of blood within 1 month prior to study start.
  14. Patient had a positive medical history for drug abuse.
  15. Patient had a known infection with human immunodeficiency virus (HIV), Hepatitis B, and/or Hepatitis C.
  16. 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.
  17. 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.
  18. Patient had any history of adverse reaction to any opiate or anesthetic agent.
  19. Patient, if male, did not agree to use an effective method of birth control between the time of screening and end of study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: fospropofol
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).
Other Names:
  • fospropofol disodium
  • LUSEDRA
  • E2083
  • GPI-15715
  • AQUAVAN
ACTIVE_COMPARATOR: propofol
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).
Other Names:
  • Disoprivan
  • propofol injectable emulsion

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Median time (minutes) to loss of consciousness from induction start (reported as median and range).
Time Frame: Day 1
Day 1

Secondary Outcome Measures

Outcome Measure
Time Frame
Median time (minutes) to induction from start of infusion (reported as median and range).
Time Frame: Day 1
Day 1
Time (minutes) to intubation from induction start (reported as median and range).
Time Frame: Day 1
Day 1
Time (minutes) to extubation from end of infusion (reported as median and range).
Time Frame: Day 1
Day 1
Time (minutes) to last suture from induction start (reported as median and range).
Time Frame: Day 1
Day 1
Time (minutes) to full awareness from end of infusion (reported as median and range).
Time Frame: Day 1
Day 1
Median time from End of Infusion to First Modified Ramsey Score of 3 (reported as median and range).
Time Frame: Day 1
Day 1

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Collaborators

PPD

Investigators

  • Study Director: James Vornov, PhD,MD, Eisai Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2002

Primary Completion (ACTUAL)

July 1, 2003

Study Completion (ACTUAL)

July 1, 2003

Study Registration Dates

First Submitted

September 13, 2005

First Submitted That Met QC Criteria

September 13, 2005

First Posted (ESTIMATE)

September 21, 2005

Study Record Updates

Last Update Posted (ESTIMATE)

June 11, 2010

Last Update Submitted That Met QC Criteria

June 10, 2010

Last Verified

June 1, 2010

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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